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Sample records for subthalamic deep brain

  1. Brain networks modulated by subthalamic nucleus deep brain stimulation.

    PubMed

    Accolla, Ettore A; Herrojo Ruiz, Maria; Horn, Andreas; Schneider, Gerd-Helge; Schmitz-Hübsch, Tanja; Draganski, Bogdan; Kühn, Andrea A

    2016-09-01

    Deep brain stimulation of the subthalamic nucleus is an established treatment for the motor symptoms of Parkinson's disease. Given the frequent occurrence of stimulation-induced affective and cognitive adverse effects, a better understanding about the role of the subthalamic nucleus in non-motor functions is needed. The main goal of this study is to characterize anatomical circuits modulated by subthalamic deep brain stimulation, and infer about the inner organization of the nucleus in terms of motor and non-motor areas. Given its small size and anatomical intersubject variability, functional organization of the subthalamic nucleus is difficult to investigate in vivo with current methods. Here, we used local field potential recordings obtained from 10 patients with Parkinson's disease to identify a subthalamic area with an analogous electrophysiological signature, namely a predominant beta oscillatory activity. The spatial accuracy was improved by identifying a single contact per macroelectrode for its vicinity to the electrophysiological source of the beta oscillation. We then conducted whole brain probabilistic tractography seeding from the previously identified contacts, and further described connectivity modifications along the macroelectrode's main axis. The designated subthalamic 'beta' area projected predominantly to motor and premotor cortical regions additional to connections to limbic and associative areas. More ventral subthalamic areas showed predominant connectivity to medial temporal regions including amygdala and hippocampus. We interpret our findings as evidence for the convergence of different functional circuits within subthalamic nucleus' portions deemed to be appropriate as deep brain stimulation target to treat motor symptoms in Parkinson's disease. Potential clinical implications of our study are illustrated by an index case where deep brain stimulation of estimated predominant non-motor subthalamic nucleus induced hypomanic behaviour. © The

  2. Tractography patterns of subthalamic nucleus deep brain stimulation.

    PubMed

    Vanegas-Arroyave, Nora; Lauro, Peter M; Huang, Ling; Hallett, Mark; Horovitz, Silvina G; Zaghloul, Kareem A; Lungu, Codrin

    2016-04-01

    Deep brain stimulation therapy is an effective symptomatic treatment for Parkinson's disease, yet the precise mechanisms responsible for its therapeutic effects remain unclear. Although the targets of deep brain stimulation are grey matter structures, axonal modulation is known to play an important role in deep brain stimulation's therapeutic mechanism. Several white matter structures in proximity to the subthalamic nucleus have been implicated in the clinical benefits of deep brain stimulation for Parkinson's disease. We assessed the connectivity patterns that characterize clinically beneficial electrodes in Parkinson's disease patients, after deep brain stimulation of the subthalamic nucleus. We evaluated 22 patients with Parkinson's disease (11 females, age 57 ± 9.1 years, disease duration 13.3 ± 6.3 years) who received bilateral deep brain stimulation of the subthalamic nucleus at the National Institutes of Health. During an initial electrode screening session, one month after deep brain stimulation implantation, the clinical benefits of each contact were determined. The electrode was localized by coregistering preoperative magnetic resonance imaging and postoperative computer tomography images and the volume of tissue activated was estimated from stimulation voltage and impedance. Brain connectivity for the volume of tissue activated of deep brain stimulation contacts was assessed using probabilistic tractography with diffusion-tensor data. Areas most frequently connected to clinically effective contacts included the thalamus, substantia nigra, brainstem and superior frontal gyrus. A series of discriminant analyses demonstrated that the strength of connectivity to the superior frontal gyrus and the thalamus were positively associated with clinical effectiveness. The connectivity patterns observed in our study suggest that the modulation of white matter tracts directed to the superior frontal gyrus and the thalamus is associated with favourable clinical

  3. Functional imaging of subthalamic nucleus deep brain stimulation in Parkinson's disease.

    PubMed

    Boertien, Tessel; Zrinzo, Ludvic; Kahan, Joshua; Jahanshahi, Marjan; Hariz, Marwan; Mancini, Laura; Limousin, Patricia; Foltynie, Thomas

    2011-08-15

    Deep brain stimulation of the subthalamic nucleus is an accepted treatment for the motor complications of Parkinson's disease. The therapeutic mechanism of action remains incompletely understood. Although the results of deep brain stimulation are similar to the results that can be obtained by lesional surgery, accumulating evidence from functional imaging and clinical neurophysiology suggests that the effects of subthalamic nucleus-deep brain stimulation are not simply the result of inhibition of subthalamic nucleus activity. Positron emission tomography/single-photon emission computed tomography has consistently demonstrated changes in cortical activation in response to subthalamic nucleus-deep brain stimulation. However, the technique has limited spatial and temporal resolution, and therefore the changes in activity of subcortical projection sites of the subthalamic nucleus (such as the globus pallidus, substantia nigra, and thalamus) are not as clear. Clarifying whether clinically relevant effects from subthalamic nucleus-deep brain stimulation in humans are mediated through inhibition or excitation of orthodromic or antidromic pathways (or both) would contribute to our understanding of the precise mechanism of action of deep brain stimulation and may allow improvements in safety and efficacy of the technique. In this review we discuss the published evidence from functional imaging studies of patients with subthalamic nucleus-deep brain stimulation to date, together with how these data inform the mechanism of action of deep brain stimulation. Copyright © 2011 Movement Disorder Society.

  4. Subthalamic nucleus deep brain stimulation improves deglutition in Parkinson's disease.

    PubMed

    Ciucci, Michelle R; Barkmeier-Kraemer, Julie M; Sherman, Scott J

    2008-04-15

    Relatively little is known about the role of the basal ganglia in human deglutition. Deep brain stimulation (DBS) affords us a model for examining deglutition in humans with known impairment of the basal ganglia. The purpose of this study was to examine the effects of subthalamic nuclei (STN) DBS on the oral and pharyngeal stages of deglutition in individuals with Parkinson's Disease (PD). It was hypothesized that DBS would be associated with improved deglutition. Within participant, comparisons were made between DBS in the ON and OFF conditions using the dependent variables: pharyngeal transit time, maximal hyoid bone excursion, oral total composite score, and pharyngeal total composite score. Significant improvement occurred for the pharyngeal composite score and pharyngeal transit time in the DBS ON condition compared with DBS OFF. Stimulation of the STN may excite thalamocortical or brainstem targets to sufficiently overcome the bradykinesia/hypokinesia associated with PD and return some pharyngeal stage motor patterns to performance levels approximating those of "normal" deglutition. However, the degree of hyoid bone excursion and oral stage measures did not improve, suggesting that these motor acts may be under the control of different sensorimotor pathways within the basal ganglia. 2007 Movement Disorder Society

  5. Differential impact of thalamic versus subthalamic deep brain stimulation on lexical processing.

    PubMed

    Krugel, Lea K; Ehlen, Felicitas; Tiedt, Hannes O; Kühn, Andrea A; Klostermann, Fabian

    2014-10-01

    Roles of subcortical structures in language processing are vague, but, interestingly, basal ganglia and thalamic Deep Brain Stimulation can go along with reduced lexical capacities. To deepen the understanding of this impact, we assessed word processing as a function of thalamic versus subthalamic Deep Brain Stimulation. Ten essential tremor patients treated with thalamic and 14 Parkinson׳s disease patients with subthalamic Deep Brain Stimulation performed an acoustic Lexical Decision Task ON and OFF stimulation. Combined analysis of task performance and event-related potentials allowed the determination of processing speed, priming effects, and N400 as neurophysiological correlate of lexical stimulus processing. 12 age-matched healthy participants acted as control subjects. Thalamic Deep Brain Stimulation prolonged word decisions and reduced N400 potentials. No comparable ON-OFF effects were present in patients with subthalamic Deep Brain Stimulation. In the latter group of patients with Parkinson' disease, N400 amplitudes were, however, abnormally low, whether under active or inactive Deep Brain Stimulation. In conclusion, performance speed and N400 appear to be influenced by state functions, modulated by thalamic, but not subthalamic Deep Brain Stimulation, compatible with concepts of thalamo-cortical engagement in word processing. Clinically, these findings specify cognitive sequels of Deep Brain Stimulation in a target-specific way.

  6. Subthalamic Nucleus Deep Brain Stimulation Changes Velopharyngeal Control in Parkinson's Disease

    ERIC Educational Resources Information Center

    Hammer, Michael J.; Barlow, Steven M.; Lyons, Kelly E.; Pahwa, Rajesh

    2011-01-01

    Purpose: Adequate velopharyngeal control is essential for speech, but may be impaired in Parkinson's disease (PD). Bilateral subthalamic nucleus deep brain stimulation (STN DBS) improves limb function in PD, but the effects on velopharyngeal control remain unknown. We tested whether STN DBS would change aerodynamic measures of velopharyngeal…

  7. Subthalamic Nucleus Deep Brain Stimulation Changes Velopharyngeal Control in Parkinson's Disease

    ERIC Educational Resources Information Center

    Hammer, Michael J.; Barlow, Steven M.; Lyons, Kelly E.; Pahwa, Rajesh

    2011-01-01

    Purpose: Adequate velopharyngeal control is essential for speech, but may be impaired in Parkinson's disease (PD). Bilateral subthalamic nucleus deep brain stimulation (STN DBS) improves limb function in PD, but the effects on velopharyngeal control remain unknown. We tested whether STN DBS would change aerodynamic measures of velopharyngeal…

  8. Weight gain following subthalamic nucleus deep brain stimulation: a PET study.

    PubMed

    Sauleau, Paul; Le Jeune, Florence; Drapier, Sophie; Houvenaghel, Jean-François; Dondaine, Thibaut; Haegelen, Claire; Lalys, Florent; Robert, Gabriel; Drapier, Dominique; Vérin, Marc

    2014-12-01

    Several hypotheses have been put forward to explain weight gain after deep brain stimulation (DBS), but none provides a fully satisfactory account of this adverse effect. We analyzed the correlation between changes in brain metabolism (using positron emission tomography [PET] imaging) and weight gain after bilateral subthalamic nucleus DBS in patients with Parkinson's disease. Body mass index was calculated and brain activity prospectively measured using 2-deoxy-2[18F]fluoro-D-glucose 3 months before and 4 months after the start of subthalamic nucleus deep brain stimulation in 23 patients with Parkinson's disease. Motor complications (United Parkinson's Disease Rating Scale [UPDRS]-IV scores) and dopaminergic medication were included in the analysis to control for their possible influence on brain metabolism. Mean ± standard deviation (SD) body mass index increased significantly by 0.8 ± 1.5 kg/m(2) (P = 0.03). Correlations were found between weight gain and changes in brain metabolism in limbic and associative areas, including the orbitofrontal cortex (Brodmann areas [BAs] 10 and 11), lateral and medial parts of the temporal lobe (BAs 20, 21, 22,39 and 42), anterior cingulate cortex (BA 32), and retrosplenial cortex (BA 30). However, we found no correlation between weight gain and metabolic changes in sensorimotor areas. These findings suggest that changes in associative and limbic processes contribute to weight gain after subthalamic nucleus DBS in Parkinson's disease.

  9. Parkinson's disease progression at 30 years: a study of subthalamic deep brain-stimulated patients.

    PubMed

    Merola, Aristide; Zibetti, Maurizio; Angrisano, Serena; Rizzi, Laura; Ricchi, Valeria; Artusi, Carlo A; Lanotte, Michele; Rizzone, Mario G; Lopiano, Leonardo

    2011-07-01

    Clinical findings in Parkinson's disease suggest that most patients progressively develop disabling non-levodopa-responsive symptoms during the course of the disease. Nevertheless, several heterogeneous factors, such as clinical phenotype, age at onset and genetic aspects may influence the long-term clinical picture. In order to investigate the main features of long-term Parkinson's disease progression, we studied a cohort of 19 subjects treated with subthalamic nucleus deep brain stimulation after >20 years of disease, reporting clinical and neuropsychological data up to a mean of 30 years from disease onset. This group of patients was characterized by an early onset of disease, with a mean age of 38.63 years at Parkinson's disease onset, which was significantly lower than in the other long-term subthalamic nucleus deep brain stimulation follow-up cohorts reported in the literature. All subjects were regularly evaluated by a complete Unified Parkinson's Disease Rating Scale, a battery of neuropsychological tests and a clinical interview, intended to assess the rate of non-levodopa-responsive symptom progression. Clinical data were available for all patients at presurgical baseline and at 1, 3 and 5 years from the subthalamic nucleus deep brain stimulation surgical procedure, while follow-up data after >7 years were additionally reported in a subgroup of 14 patients. The clinical and neuropsychological performance progressively worsened during the course of follow-up; 64% of patients gradually developed falls, 86% dysphagia, 57% urinary incontinence and 43% dementia. A progressive worsening of motor symptoms was observed both in 'medication-ON' condition and in 'stimulation-ON' condition, with a parallel reduction in the synergistic effect of 'medication-ON/stimulation-ON' condition. Neuropsychological data also showed a gradual decline in the performances of all main cognitive domains, with an initial involvement of executive functions, followed by the impairment

  10. Subthalamic nucleus deep brain stimulation in early stage Parkinson's disease.

    PubMed

    Charles, David; Konrad, Peter E; Neimat, Joseph S; Molinari, Anna L; Tramontana, Michael G; Finder, Stuart G; Gill, Chandler E; Bliton, Mark J; Kao, Chris; Phibbs, Fenna T; Hedera, Peter; Salomon, Ronald M; Cannard, Kevin R; Wang, Lily; Song, Yanna; Davis, Thomas L

    2014-07-01

    Deep brain stimulation (DBS) is an effective and approved therapy for advanced Parkinson's disease (PD), and a recent study suggests efficacy in mid-stage disease. This manuscript reports the results of a pilot trial investigating preliminary safety and tolerability of DBS in early PD. Thirty subjects with idiopathic PD (Hoehn & Yahr Stage II off medication), age 50-75, on medication ≥6 months but ≤4 years, and without motor fluctuations or dyskinesias were randomized to optimal drug therapy (ODT) (n = 15) or DBS + ODT (n = 15). Co-primary endpoints were the time to reach a 4-point worsening from baseline in the UPDRS-III off therapy and the change in levodopa equivalent daily dose from baseline to 24 months. As hypothesized, the mean UPDRS total and part III scores were not significantly different on or off therapy at 24 months. Medication requirements in the DBS + ODT group were lower at all time points with a maximal difference at 18 months. With a few exceptions, differences in neuropsychological functioning were not significant. Two subjects in the DBS + ODT group suffered serious adverse events; remaining adverse events were mild or transient. This study demonstrates that subjects with early stage PD will enroll in and complete trials testing invasive therapies and provides preliminary evidence that DBS is well tolerated in early PD. The results of this trial provide the data necessary to design a large, phase III, double-blind, multicenter trial investigating the safety and efficacy of DBS in early PD. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Addiction in Parkinson's disease: impact of subthalamic nucleus deep brain stimulation.

    PubMed

    Witjas, Tatiana; Baunez, Christelle; Henry, Jean Marc; Delfini, Marie; Regis, Jean; Cherif, André Ali; Peragut, Jean Claude; Azulay, Jean Philippe

    2005-08-01

    In Parkinson's disease, dopamine dysregulation syndrome (DDS) is characterized by severe dopamine addiction and behavioral disorders such as manic psychosis, hypersexuality, pathological gambling, and mood swings. Here, we describe the case of 2 young parkinsonian patients suffering from disabling motor fluctuations and dyskinesia associated with severe DDS. In addition to alleviating the motor disability in both patients, subthalamic nucleus (STN) deep brain stimulation greatly reduced the behavioral disorders as well as completely abolished the addiction to dopaminergic treatment. Dopaminergic addiction in patients with Parkinson's disease, therefore, does not constitute an obstacle to high-frequency STN stimulation, and this treatment may even cure the addiction.

  12. Mood Response to Deep Brain Stimulation of the Subthalamic Nucleus in Parkinson Disease

    PubMed Central

    Campbell, Meghan C.; Black, Kevin J.; Weaver, Patrick M.; Lugar, Heather M.; Videen, Tom O.; Tabbal, Samer D.; Karimi, Morvarid; Perlmutter, Joel S.; Hershey, Tamara

    2012-01-01

    Deep brain stimulation of the subthalamic nucleus (STN DBS) in Parkinson disease (PD) improves motor function but has variable effects on mood. Little is known about the relationship between electrode contact location and mood response. We identified the anatomical location of electrode contacts and measured mood response to stimulation with the Visual Analog Scale in 24 STN DBS PD patients. Participants reported greater positive mood, decreased anxiety and apathy with bilateral and unilateral stimulation. Left DBS improved mood more than right DBS. Right DBS-induced increase in positive mood was related to more medial and dorsal contact locations. These results highlight the functional heterogeneity of the STN. PMID:22450611

  13. [Psychiatric symptoms of Parkinson's disease following deep brain stimulation surgery on the subthalamic nucleus].

    PubMed

    Salvador-Aguiar, C; Menéndez-Guisasola, L; Blázquez-Estrada, M; Fernández-González, F; Seijo-Fernández, F

    To review the increasing number of papers that report diverse neuropsychiatric disorders that happen in patients diagnosed of Parkinson's disease submitted to brain deep stimulation of subthalamic nuclei with high frequency current. It is a fact the need to evaluate carefully all the patients who have to submit to this surgical procedure analyzing previous psychiatric history, and the possible appearance of psychiatric sphere symptoms after surgery. The acute depression and the euphoric moods (than can occur immediately after surgery) and major depression, obsession, widespread anxiety and substance abuse (among those of more delayed appearance) constitute examples of this pathology. The treatment of previous psychiatric disorders is forced in all cases and specially relevant in the major depression when suicide ideas coexist. Information that allow to predict the risk of developing depressive disorders in the postoperative period does not exist at present time, though it is more predictable that it happens in those patients with previous severe depressive history. In general, euphoric moods, apathy and depression, usually are transient and of multifactorial origin that includes the existence of endogenous predisposition, the change to an independence pattern after surgery, the psychotropic effect of levodopa, and the high frequency current stimulation effect on the non motor structures target and in the adjacent regions. It must be outlined that it is possible the appearance of psychotic symptoms after brain deep stimulation of subthalamic nuclei in patients with ideal results on motor disability.

  14. Intensive Voice Treatment (LSVT[R]LOUD) for Parkinson's Disease Following Deep Brain Stimulation of the Subthalamic Nucleus

    ERIC Educational Resources Information Center

    Spielman, Jennifer; Mahler, Leslie; Halpern, Angela; Gilley, Phllip; Klepitskaya, Olga; Ramig, Lorraine

    2011-01-01

    Purpose: Intensive voice therapy (LSVT[R]LOUD) can effectively manage voice and speech symptoms associated with idiopathic Parkinson disease (PD). This small-group study evaluated voice and speech in individuals with and without deep brain stimulation of the subthalamic nucleus (STN-DBS) before and after LSVT LOUD, to determine whether outcomes…

  15. Pitch Variability in Patients with Parkinson's Disease: Effects of Deep Brain Stimulation of Caudal Zona Incerta and Subthalamic Nucleus

    ERIC Educational Resources Information Center

    Karlsson, Fredrik; Olofsson, Katarina; Blomstedt, Patric; Linder, Jan; van Doorn, Jan

    2013-01-01

    Purpose: The purpose of the present study was to examine the effect of deep brain stimulation (DBS) of the subthalamic nucleus (STN) and the caudal zona incerta (cZi) pitch characteristics of connected speech in patients with Parkinson's disease (PD). Method: The authors evaluated 16 patients preoperatively and 12 months after DBS surgery. Eight…

  16. Pitch Variability in Patients with Parkinson's Disease: Effects of Deep Brain Stimulation of Caudal Zona Incerta and Subthalamic Nucleus

    ERIC Educational Resources Information Center

    Karlsson, Fredrik; Olofsson, Katarina; Blomstedt, Patric; Linder, Jan; van Doorn, Jan

    2013-01-01

    Purpose: The purpose of the present study was to examine the effect of deep brain stimulation (DBS) of the subthalamic nucleus (STN) and the caudal zona incerta (cZi) pitch characteristics of connected speech in patients with Parkinson's disease (PD). Method: The authors evaluated 16 patients preoperatively and 12 months after DBS surgery. Eight…

  17. Intensive Voice Treatment (LSVT[R]LOUD) for Parkinson's Disease Following Deep Brain Stimulation of the Subthalamic Nucleus

    ERIC Educational Resources Information Center

    Spielman, Jennifer; Mahler, Leslie; Halpern, Angela; Gilley, Phllip; Klepitskaya, Olga; Ramig, Lorraine

    2011-01-01

    Purpose: Intensive voice therapy (LSVT[R]LOUD) can effectively manage voice and speech symptoms associated with idiopathic Parkinson disease (PD). This small-group study evaluated voice and speech in individuals with and without deep brain stimulation of the subthalamic nucleus (STN-DBS) before and after LSVT LOUD, to determine whether outcomes…

  18. Predicting quality of life outcomes after subthalamic nucleus deep brain stimulation

    PubMed Central

    Cooper, Scott E.; Griffith, Sandra D.; Machado, Andre G.

    2014-01-01

    Objectives: To examine disease, treatment, cognitive, and psychological factors associated with quality of life (QoL) before and after surgery and assess the ability to predict QoL outcomes. Methods: We identified a retrospective, cross-sectional sample of 85 patients with Parkinson disease who underwent subthalamic deep brain stimulation (DBS). Patients' QoL was categorized as “improved” and “stable/worsened” using reliable change indices. Univariate correlational analyses identified relationships between Parkinson's Disease Questionnaire–39 ratings and disease (Unified Parkinson's Disease Rating Scale–III [UPDRS-III] motor scores on and off medications, disease duration), treatment (medication burden, unilateral vs bilateral DBS), cognitive (neuropsychological battery), and psychological (depression) variables. Step-wise multiple linear regression and logistic regression models included selected preoperative variables to predict change in QoL ratings and QoL outcome after surgery. Results: Fifty-one percent of patients reported clinically significant improvements in QoL while 47% reported stable QoL and 2% worsened. Motor scores (UPDRS-III) were not relevant to QoL changes, potentially because of the rarity of poor motor outcomes, while single-trial learning and depression scores were the most important variables in predicting QoL changes. There was a subtle additional benefit to undergoing bilateral subthalamic nucleus DBS. Conclusions: The findings provide greater insight into the nonmotor features that contribute to the success of subthalamic nucleus DBS procedures from the patient's perspective and raise questions about the treatment focus and emphasis on symptom profiles in DBS candidacy evaluations. PMID:25274851

  19. Evidence of subthalamic PGO-like waves during REM sleep in humans: a deep brain polysomnographic study.

    PubMed

    Fernández-Mendoza, Julio; Lozano, Beatriz; Seijo, Fernando; Santamarta-Liébana, Elena; Ramos-Platón, Maria José; Vela-Bueno, Antonio; Fernández-González, Fernando

    2009-09-01

    The aim of this study was to examine whether the subthalamic nucleus (STN) plays a role in the transmission of PGO-like waves during REM sleep in humans. Simultaneous recordings from deep brain electrodes to record local field potentials (LFPs), and standard polysomnography to ascertain sleep/wake states. Main Hospital, department of clinical neurophysiology sleep laboratory. 12 individuals with Parkinson's disease, with electrodes implanted in the STN; and, as a control for localization purposes, 4 cluster headache patients with electrodes implanted in the posterior hypothalamus. All subjects underwent functional neurosurgery for implantation of deep brain stimulation electrodes. Sharp, polarity-reversed LFPs were recorded within the STN during REM sleep in humans. These subthalamic PGO-like waves (2-3 Hz, 80-200 pV, and 300-500 msec) appeared during REM epochs as singlets or in clusters of 3-13 waves. During the pre-REM period, subthalamic PGO-like waves were temporally related to drops in the submental electromyogram and/or onset of muscular atonia. Clusters of PGO-like waves occurred typically before and during the bursts of rapid eye movements and were associated with an enhancement in fast (15-35 Hz) subthalamic oscillatory activity. Subthalamic PGO-like waves can be recorded during pre-REM and REM sleep in humans. Our data suggest that the STN may play an active role in an ascending activating network implicated in the transmission of PGO waves during REM sleep in humans.

  20. Targeting of the Subthalamic Nucleus for Deep Brain Stimulation: A Survey Among Parkinson Disease Specialists.

    PubMed

    Hamel, Wolfgang; Köppen, Johannes A; Alesch, François; Antonini, Angelo; Barcia, Juan A; Bergman, Hagai; Chabardes, Stephan; Contarino, Maria Fiorella; Cornu, Philippe; Demmel, Walter; Deuschl, Günther; Fasano, Alfonso; Kühn, Andrea A; Limousin, Patricia; McIntyre, Cameron C; Mehdorn, H Maximilian; Pilleri, Manuela; Pollak, Pierre; Rodríguez-Oroz, Maria C; Rumià, Jordi; Samuel, Michael; Timmermann, Lars; Valldeoriola, Francesc; Vesper, Jan; Visser-Vandewalle, Veerle; Volkmann, Jens; Lozano, Andres M

    2017-03-01

    Deep brain stimulation within or adjacent to the subthalamic nucleus (STN) represents the most common stereotactic procedure performed for Parkinson disease. Better STN imaging is often regarded as a requirement for improving stereotactic targeting. However, it is unclear whether there is consensus about the optimal target. To obtain an expert opinion on the site regarded optimal for "STN stimulation," movement disorder specialists were asked to indicate their preferred position for an active contact on hard copies of the Schaltenbrand and Wahren atlas depicting the STN in all 3 planes. This represented an idealized setting, and it mimicked optimal imaging for direct target definition in a perfectly delineated STN. The suggested targets were heterogeneous, although some clustering was observed in the dorsolateral STN and subthalamic area. In particular, in the anteroposterior direction, the intended targets differed to a great extent. Most of the indicated targets are thought to also result in concomitant stimulation of structures adjacent to the STN, including the zona incerta, fields of Forel, and internal capsule. This survey illustrates that most sites regarded as optimal for STN stimulation are close to each other, but there appears to be no uniform perception of the optimal anatomic target, possibly influencing surgical results. The anatomic sweet zone for STN stimulation needs further specification, as this information is likely to make magnetic resonance imaging-based target definition less variable when applied to individual patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Subthalamic nucleus deep brain stimulation affects distractor interference in auditory working memory.

    PubMed

    Camalier, Corrie R; Wang, Alice Y; McIntosh, Lindsey G; Park, Sohee; Neimat, Joseph S

    2017-03-01

    Computational and theoretical accounts hypothesize the basal ganglia play a supramodal "gating" role in the maintenance of working memory representations, especially in preservation from distractor interference. There are currently two major limitations to this account. The first is that supporting experiments have focused exclusively on the visuospatial domain, leaving questions as to whether such "gating" is domain-specific. The second is that current evidence relies on correlational measures, as it is extremely difficult to causally and reversibly manipulate subcortical structures in humans. To address these shortcomings, we examined non-spatial, auditory working memory performance during reversible modulation of the basal ganglia, an approach afforded by deep brain stimulation of the subthalamic nucleus. We found that subthalamic nucleus stimulation impaired auditory working memory performance, specifically in the group tested in the presence of distractors, even though the distractors were predictable and completely irrelevant to the encoding of the task stimuli. This study provides key causal evidence that the basal ganglia act as a supramodal filter in working memory processes, further adding to our growing understanding of their role in cognition.

  2. Evidence of Subthalamic PGO-like Waves During REM Sleep in Humans: A Deep Brain Polysomnographic Study

    PubMed Central

    Fernández-Mendoza, Julio; Lozano, Beatriz; Seijo, Fernando; Santamarta-Liébana, Elena; Ramos-Platón, Maria José; Vela-Bueno, Antonio; Fernández-González, Fernando

    2009-01-01

    Study Objectives: The aim of this study was to examine whether the subthalamic nucleus (STN) plays a role in the transmission of PGO-like waves during REM sleep in humans. Design: Simultaneous recordings from deep brain electrodes to record local field potentials (LFPs), and standard polysomnography to ascertain sleep/wake states. Setting: Main Hospital, department of clinical neurophysiology sleep laboratory. Participants: 12 individuals with Parkinson's disease, with electrodes implanted in the STN; and, as a control for localization purposes, 4 cluster headache patients with electrodes implanted in the posterior hypothalamus. Interventions: All subjects underwent functional neurosurgery for implantation of deep brain stimulation electrodes. Results: Sharp, polarity-reversed LFPs were recorded within the STN during REM sleep in humans. These subthalamic PGO-like waves (2–3 Hz, 80–200 μV, and 300–500 msec) appeared during REM epochs as singlets or in clusters of 3–13 waves. During the pre-REM period, subthalamic PGO-like waves were temporally related to drops in the submental electromyogram and/or onset of muscular atonia. Clusters of PGO-like waves occurred typically before and during the bursts of rapid eye movements and were associated with an enhancement in fast (15–35 Hz) subthalamic oscillatory activity. Conclusion: Subthalamic PGO-like waves can be recorded during pre-REM and REM sleep in humans. Our data suggest that the STN may play an active role in an ascending activating network implicated in the transmission of PGO waves during REM sleep in humans. Citation: Fernández-Mendoza J; Lozano B; Seijo F; Santamarta-Liébana E; Ramos-Platón MJ; Vela-Bueno A; Fernández-González F. Evidence of subthalamic PGO-like waves during REM sleep in humans: a deep brain polysomnographic study. SLEEP 2009;32(9):1117-1126. PMID:19750916

  3. The effects of subthalamic deep brain stimulation on metaphor comprehension and language abilities in Parkinson's disease.

    PubMed

    Tremblay, Christina; Macoir, Joël; Langlois, Mélanie; Cantin, Léo; Prud'homme, Michel; Monetta, Laura

    2015-02-01

    The effects of subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson's disease (PD) on different language abilities are still controversial and its impact on high-level language abilities such as metaphor comprehension has been overlooked. The aim of this study was to determine the effects of STN electrical stimulation on metaphor comprehension and language abilities such as lexical and semantic capacities. Eight PD individuals with bilateral STN-DBS were first evaluated OFF-DBS and, at least seven weeks later, ON-DBS. Performance on metaphor comprehension, lexical decision, word association and verbal fluency tasks were compared ON and OFF-DBS in addition to motor symptoms evaluation. STN stimulation had a significant beneficial effect on motor symptoms in PD. However, this stimulation did not have any effect on metaphor comprehension or any other cognitive ability evaluated in this study. These outcomes suggest that STN stimulation may have dissociable effects on motor and language functions.

  4. Deep brain stimulation of the subthalamic nucleus in Parkinson's disease: surgical technique, tips, tricks and complications.

    PubMed

    Kocabicak, Ersoy; Temel, Yasin

    2013-11-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become a frequently performed surgery in patients with advanced Parkinson's disease. The technique has been further refined throughout the years by improved imaging techniques, advanced neurophysiological recording possibilities, and advances in hardware and software technology. In addition, the complications, which can be divided into surgery-related, target-related, and hardware-related complications, were better recognised and managed. In this review, we describe our experience specifically with the surgery of STN DBS in the light of the existing literature. Tips and tricks, complications and their management are the main elements of this article. In addition, we provide scientific information from our research and other groups in specific sections. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Parkinson's disease patients with bilateral subthalamic deep brain stimulation gain weight.

    PubMed

    Macia, Frédéric; Perlemoine, Caroline; Coman, Irène; Guehl, Dominique; Burbaud, Pierre; Cuny, Emmanuel; Gin, Henri; Rigalleau, Vincent; Tison, François

    2004-02-01

    Weight, body mass index (BMI) and energy expenditure/energy intake (EE/EI) was studied in 19 Parkinson's disease (PD) patients after subthalamic deep brain stimulation (STN-DBS) versus 14 nonoperated ones. Operated patients had a significant weight gain (WG, + 9.7 +/- 7 kg) and BMI increase (+ 4.7 kg/m2). The fat mass was higher after STN-DBS. Resting EE (REE; offdrug/ON stimulation) was significantly decreased in STN-DBS patients, while their daily energy expenditure (DEI) was not significantly different. A significant correlation was found among WG, BMI increase, and pre-operative levodopa-equivalent daily dose, their reduction after STN-DBS, and the differential REE related to stimulation and the REE in the offdrug/OFF stimulation condition. In conclusion, STN-DBS in PD induces a significant WG associated with a reduction in REE without DEI adjustment.

  6. Treatment of dysarthria following subthalamic nucleus deep brain stimulation for Parkinson’s disease

    PubMed Central

    Tripoliti, Elina; Strong, Laura; Hickey, Freya; Foltynie, Tom; Zrinzo, Ludvic; Candelario, Joseph; Hariz, Marwan; Limousin, Patricia

    2011-01-01

    Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an established treatment for patients with Parkinson’s disease (PD). Speech impairment is a frequent side effect of the surgery. This study examined the efficacy of an intensive speech treatment (the Lee Silverman Voice Treatment, LSVT) on dysarthria after STN-DBS. The LSVT was administered in ten patients with STN-DBS (surgical group) and ten patients without (medical group). Patients were assessed before, immediately after and six months following the speech treatment using sustained phonation, a speech intelligibility scale and monologue. Vocal loudness, speech intelligibility and perceptual ratings were the primary outcome measures. Vocal loudness and perceptual scores improved significantly across tasks for the medical group only. Speech intelligibility did not significantly change for either group. Results in the surgical group were variable with some patients deteriorating. Treatment of dysarthria following STN-DBS needs further investigation due to the variable response to LSVT. PMID:21953693

  7. Deep brain stimulation of the subthalamic nucleus improves pain in Parkinson's disease.

    PubMed

    Pellaprat, Jean; Ory-Magne, Fabienne; Canivet, Cindy; Simonetta-Moreau, Marion; Lotterie, Jean-Albert; Radji, Fatai; Arbus, Christophe; Gerdelat, Angélique; Chaynes, Patrick; Brefel-Courbon, Christine

    2014-06-01

    In Parkinson's disease (PD), chronic pain is a common symptom which markedly affects the quality of life. Some physiological arguments proposed that Deep Brain Stimulation of the Subthalamic Nucleus (STN-DBS) could improve pain in PD. We investigated in 58 PD patients the effect of STN-DBS on pain using the short McGill Pain Questionnaire and other pain parameters such as the Bodily discomfort subscore of the Parkinson's disease Questionnaire 39 and the Unified Parkinson's Disease Rating Scale section II (UPDRS II) item 17. All pain scores were significantly improved 12 months after STN-DBS. This improvement was not correlated with motor improvement, depression scores or L-Dopa reduction. STN-DBS induced a substantial beneficial effect on pain in PD, independently of its motor effects and mood status of patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Sedation with α2 Agonist Dexmedetomidine During Unilateral Subthalamic Nucleus Deep Brain Stimulation: A Preliminary Report.

    PubMed

    Morace, Roberta; De Angelis, Michelangelo; Aglialoro, Emiliano; Maucione, Gianni; Cavallo, LuigiMaria; Solari, Domenico; Modugno, Nicola; Santilli, Marco; Esposito, Vincenzo; Aloj, Fulvio

    2016-05-01

    The α2 agonist dexmedetomidine (DEX) is an anesthetic agent that can provide sedation and analgesia without respiratory depression or changes in neuronal activity during microrecordings. The aim of our study was to confirm the efficacy and safety of anesthesia with DEX for unilateral deep brain stimulation of the subthalamic nucleus (STN) in patients with Parkinson disease. In 2013 and 2014, a series of 11 consecutive patients received continuous low-dose DEX infusion during unilateral deep brain stimulation of the STN. Intraoperative microrecordings, stimulation results, and patient reaction times in executing verbal and motor tasks were retrospectively analyzed. Functional outcomes were evaluated by comparing preoperative and 1-year postoperative Unified Parkinson's Disease Rating Scale Part III scores. Typical activity of the STN was recorded in all patients, and the delay in the execution of both motor and verbal tasks was ≤2 seconds. No hemorrhagic complications occurred, and no postoperative side effects were observed. The mean percentage of Unified Parkinson's Disease Rating Scale Part III improvement at last follow-up was 39.01% (range, 23.70%-55.60%). The mean percentage of levodopa equivalent dose reduction was 45.86% (range, 21.50%-65.70%). The results of our study confirm that the use of DEX in managing patients with Parkinson disease during unilateral deep brain stimulation of the STN is safe and effective and can be considered a promising option for sedation during this type of procedure. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. The Impact of Subthalamic Deep Brain Stimulation on Sleep-Wake Behavior: A Prospective Electrophysiological Study in 50 Parkinson Patients.

    PubMed

    Baumann-Vogel, Heide; Imbach, Lukas L; Sürücü, Oguzkan; Stieglitz, Lennart; Waldvogel, Daniel; Baumann, Christian R; Werth, Esther

    2017-05-01

    This prospective observational study was designed to systematically examine the effect of subthalamic deep brain stimulation (DBS) on subjective and objective sleep-wake parameters in Parkinson patients. In 50 consecutive Parkinson patients undergoing subthalamic DBS, we assessed motor symptoms, medication, the position of DBS electrodes within the subthalamic nucleus (STN), subjective sleep-wake parameters, 2-week actigraphy, video-polysomnography studies, and sleep electroencepahalogram frequency and dynamics analyses before and 6 months after surgery. Subthalamic DBS improved not only motor symptoms and reduced daily intake of dopaminergic agents but also enhanced subjective sleep quality and reduced sleepiness (Epworth Sleepiness Scale: -2.1 ± 3.8, p < .001). Actigraphy recordings revealed longer bedtimes (+1:06 ± 0:51 hours, p < .001) without shifting of circadian timing. Upon polysomnography, we observed an increase in sleep efficiency (+5.2 ± 17.6%, p = .005) and deep sleep (+11.2 ± 32.2 min, p = .017) and increased accumulation of slow-wave activity over the night (+41.0 ± 80.0%, p = .005). Rapid eye movement sleep features were refractory to subthalamic DBS, and the dynamics of sleep as assessed by state space analyses did not normalize. Increased sleep efficiency was associated with active electrode contact localization more distant from the ventral margin of the left subthalamic nucleus. Subthalamic DBS deepens and consolidates nocturnal sleep and improves daytime wakefulness in Parkinson patients, but several outcomes suggest that it does not normalize sleep. It remains elusive whether modulated activity in the STN directly contributes to changes in sleep-wake behavior, but dorsal positioning of electrodes within the STN is linked to improved sleep-wake outcomes.

  10. Current steering to activate targeted neural pathways during deep brain stimulation of the subthalamic region

    PubMed Central

    Chaturvedi, Ashutosh; Foutz, Thomas J.; McIntyre, Cameron C.

    2012-01-01

    Deep brain stimulation (DBS) has steadily evolved into an established surgical therapy for numerous neurological disorders, most notably Parkinson’s disease (PD). Traditional DBS technology relies on voltage-controlled stimulation with a single source; however, recent engineering advances are providing current-controlled devices with multiple independent sources. These new stimulators deliver constant current to the brain tissue, irrespective of impedance changes that occur around the electrode, and enable more specific steering of current towards targeted regions of interest. In this study, we examined the impact of current steering between multiple electrode contacts to directly activate three distinct neural populations in the subthalamic region commonly stimulated for the treatment of PD: projection neurons of the subthalamic nucleus (STN), globus pallidus internus (GPi) fibers of the lenticular fasiculus, and internal capsule (IC) fibers of passage. We used three-dimensional finite element electric field models, along with detailed multi-compartment cable models of the three neural populations to determine their activations using a wide range of stimulation parameter settings. Our results indicate that selective activation of neural populations largely depends on the location of the active electrode(s). Greater activation of the GPi and STN populations (without activating any side-effect related IC fibers) was achieved by current steering with multiple independent sources, compared to a single current source. Despite this potential advantage, it remains to be seen if these theoretical predictions result in a measurable clinical effect that outweighs the added complexity of the expanded stimulation parameter search space generated by the more flexible technology. PMID:22277548

  11. Reduced Verbal Fluency following Subthalamic Deep Brain Stimulation: A Frontal-Related Cognitive Deficit?

    PubMed Central

    Houvenaghel, Jean-François; Le Jeune, Florence; Dondaine, Thibaut; Esquevin, Aurore; Robert, Gabriel Hadrien; Péron, Julie; Haegelen, Claire; Drapier, Sophie; Jannin, Pierre; Lozachmeur, Clément; Argaud, Soizic; Duprez, Joan; Drapier, Dominique; Vérin, Marc; Sauleau, Paul

    2015-01-01

    Objective The decrease in verbal fluency in patients with Parkinson’s disease (PD) undergoing subthalamic nucleus deep brain stimulation (STN-DBS) is usually assumed to reflect a frontal lobe-related cognitive dysfunction, although evidence for this is lacking. Methods To explore its underlying mechanisms, we combined neuropsychological, psychiatric and motor assessments with an examination of brain metabolism using F-18 fluorodeoxyglucose positron emission tomography, in 26 patients with PD, 3 months before and after surgery. We divided these patients into two groups, depending on whether or not they exhibited a postoperative deterioration in either phonemic (10 patients) or semantic (8 patients) fluency. We then compared the STN-DBS groups with and without verbal deterioration on changes in clinical measures and brain metabolism. Results We did not find any neuropsychological change supporting the presence of an executive dysfunction in patients with a deficit in either phonemic or semantic fluency. Similarly, a comparison of patients with or without impaired fluency on brain metabolism failed to highlight any frontal areas involved in cognitive functions. However, greater changes in cognitive slowdown and apathy were observed in patients with a postoperative decrease in verbal fluency. Conclusions These results suggest that frontal lobe-related cognitive dysfunction could play only a minor role in the postoperative impairment of phonemic or semantic fluency, and that cognitive slowdown and apathy could have a more decisive influence. Furthermore, the phonemic and semantic impairments appeared to result from the disturbance of distinct mechanisms. PMID:26448131

  12. Deep brain stimulation of the subthalamic nucleus modulates sensitivity to decision outcome value in Parkinson’s disease

    NASA Astrophysics Data System (ADS)

    Seymour, Ben; Barbe, Michael; Dayan, Peter; Shiner, Tamara; Dolan, Ray; Fink, Gereon R.

    2016-09-01

    Deep brain stimulation (DBS) of the subthalamic nucleus in Parkinson’s disease is known to cause a subtle but important adverse impact on behaviour, with impulsivity its most widely reported manifestation. However, precisely which computational components of the decision process are modulated is not fully understood. Here we probe a number of distinct subprocesses, including temporal discount, outcome utility, instrumental learning rate, instrumental outcome sensitivity, reward-loss trade-offs, and perseveration. We tested 22 Parkinson’s Disease patients both on and off subthalamic nucleus deep brain stimulation (STN-DBS), while they performed an instrumental learning task involving financial rewards and losses, and an inter-temporal choice task for financial rewards. We found that instrumental learning performance was significantly worse following stimulation, due to modulation of instrumental outcome sensitivity. Specifically, patients became less sensitive to decision values for both rewards and losses, but without any change to the learning rate or reward-loss trade-offs. However, we found no evidence that DBS modulated different components of temporal impulsivity. In conclusion, our results implicate the subthalamic nucleus in a modulation of outcome value in experience-based learning and decision-making in Parkinson’s disease, suggesting a more pervasive role of the subthalamic nucleus in the control of human decision-making than previously thought.

  13. Deep brain stimulation of the subthalamic nucleus modulates sensitivity to decision outcome value in Parkinson’s disease

    PubMed Central

    Seymour, Ben; Barbe, Michael; Dayan, Peter; Shiner, Tamara; Dolan, Ray; Fink, Gereon R.

    2016-01-01

    Deep brain stimulation (DBS) of the subthalamic nucleus in Parkinson’s disease is known to cause a subtle but important adverse impact on behaviour, with impulsivity its most widely reported manifestation. However, precisely which computational components of the decision process are modulated is not fully understood. Here we probe a number of distinct subprocesses, including temporal discount, outcome utility, instrumental learning rate, instrumental outcome sensitivity, reward-loss trade-offs, and perseveration. We tested 22 Parkinson’s Disease patients both on and off subthalamic nucleus deep brain stimulation (STN-DBS), while they performed an instrumental learning task involving financial rewards and losses, and an inter-temporal choice task for financial rewards. We found that instrumental learning performance was significantly worse following stimulation, due to modulation of instrumental outcome sensitivity. Specifically, patients became less sensitive to decision values for both rewards and losses, but without any change to the learning rate or reward-loss trade-offs. However, we found no evidence that DBS modulated different components of temporal impulsivity. In conclusion, our results implicate the subthalamic nucleus in a modulation of outcome value in experience-based learning and decision-making in Parkinson’s disease, suggesting a more pervasive role of the subthalamic nucleus in the control of human decision-making than previously thought. PMID:27624437

  14. Subthalamic Nucleus Deep Brain Stimulation Alters Prefrontal Correlates of Emotion Induction.

    PubMed

    Bick, Sarah K B; Folley, Bradley S; Mayer, Jutta S; Park, Sohee; Charles, P David; Camalier, Corrie R; Pallavaram, Srivatsan; Konrad, Peter E; Neimat, Joseph S

    2017-04-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor symptoms in advanced Parkinson's disease. STN DBS may also affect emotion, possibly by impacting a parallel limbic cortico-striatal circuit. The objective of this study was to investigate changes in prefrontal cortical activity related to DBS during an emotion induction task. We used near infrared spectroscopy to monitor prefrontal cortex hemodynamic changes during an emotion induction task. Seven DBS patients were tested sequentially in the stimulation-on and stimulation-off states while on dopaminergic medication. Patients watched a series of positive, negative, and neutral videos. The general linear model was used to compare prefrontal oxygenated hemoglobin concentration between DBS states. Deep brain stimulation was correlated with prefrontal oxygenated hemoglobin changes relative to the stimulation off state in response to both positive and negative videos. These changes were specific to emotional stimuli and were not seen during neutral stimuli. These results suggest that STN stimulation influences the prefrontal cortical representation of positive and negative emotion induction. © 2016 International Neuromodulation Society.

  15. A novel lead design enables selective deep brain stimulation of neural populations in the subthalamic region

    NASA Astrophysics Data System (ADS)

    van Dijk, Kees J.; Verhagen, Rens; Chaturvedi, Ashutosh; McIntyre, Cameron C.; Bour, Lo J.; Heida, Ciska; Veltink, Peter H.

    2015-08-01

    Objective. The clinical effects of deep brain stimulation (DBS) of the subthalamic nucleus (STN-DBS) as a treatment for Parkinson’s disease are sensitive to the location of the DBS lead within the STN. New high density (HD) lead designs have been created which are hypothesized to provide additional degrees of freedom in shaping the stimulating electric field. The objective of this study is to compare the performances of a new HD lead with a conventional cylindrical contact (CC) lead. Approach. A computational model, consisting of a finite element electric field model combined with multi-compartment neuron and axon models representing different neural populations in the subthalamic region, was used to evaluate the two leads. We compared ring-mode and steering-mode stimulation with the HD lead to single contact stimulation with the CC lead. These stimulation modes were tested for the lead: (1) positioned in the centroid of the STN, (2) shifted 1 mm towards the internal capsule (IC), and (3) shifted 2 mm towards the IC. Under these conditions, we quantified the number of STN neurons that were activated without activating IC fibers, which are known to cause side-effects. Main results. The modeling results show that the HD lead is able to mimic the stimulation effect of the CC lead. Additionally, in steering-mode stimulation there was a significant increase of activated STN neurons compared to the CC mode. Significance. From the model simulations we conclude that the HD lead in steering-mode with optimized stimulation parameter selection can stimulate more STN cells. Next, the clinical impact of the increased number of activated STN cells should be tested and balanced across the increased complexity of identifying the optimized stimulation parameter settings for the HD lead.

  16. A novel lead design enables selective deep brain stimulation of neural populations in the subthalamic region.

    PubMed

    van Dijk, Kees J; Verhagen, Rens; Chaturvedi, Ashutosh; McIntyre, Cameron C; Bour, Lo J; Heida, Ciska; Veltink, Peter H

    2015-08-01

    The clinical effects of deep brain stimulation (DBS) of the subthalamic nucleus (STN-DBS) as a treatment for Parkinson's disease are sensitive to the location of the DBS lead within the STN. New high density (HD) lead designs have been created which are hypothesized to provide additional degrees of freedom in shaping the stimulating electric field. The objective of this study is to compare the performances of a new HD lead with a conventional cylindrical contact (CC) lead. A computational model, consisting of a finite element electric field model combined with multi-compartment neuron and axon models representing different neural populations in the subthalamic region, was used to evaluate the two leads. We compared ring-mode and steering-mode stimulation with the HD lead to single contact stimulation with the CC lead. These stimulation modes were tested for the lead: (1) positioned in the centroid of the STN, (2) shifted 1 mm towards the internal capsule (IC), and (3) shifted 2 mm towards the IC. Under these conditions, we quantified the number of STN neurons that were activated without activating IC fibers, which are known to cause side-effects. The modeling results show that the HD lead is able to mimic the stimulation effect of the CC lead. Additionally, in steering-mode stimulation there was a significant increase of activated STN neurons compared to the CC mode. From the model simulations we conclude that the HD lead in steering-mode with optimized stimulation parameter selection can stimulate more STN cells. Next, the clinical impact of the increased number of activated STN cells should be tested and balanced across the increased complexity of identifying the optimized stimulation parameter settings for the HD lead.

  17. Deep Brain Stimulation Frequency of the Subthalamic Nucleus Affects Phonemic and Action Fluency in Parkinson's Disease.

    PubMed

    Fagundes, Valéria de Carvalho; Rieder, Carlos R M; da Cruz, Aline Nunes; Beber, Bárbara Costa; Portuguez, Mirna Wetters

    2016-01-01

    Introduction. Deep brain stimulation of the subthalamic nucleus (STN-DBS) in Parkinson's disease (PD) has been linked to a decline in verbal fluency. The decline can be attributed to surgical effects, but the relative contributions of the stimulation parameters are not well understood. This study aimed to investigate the impact of the frequency of STN-DBS on the performance of verbal fluency tasks in patients with PD. Methods. Twenty individuals with PD who received bilateral STN-DBS were evaluated. Their performances of verbal fluency tasks (semantic, phonemic, action, and unconstrained fluencies) upon receiving low-frequency (60 Hz) and high-frequency (130 Hz) STN-DBS were assessed. Results. The performances of phonemic and action fluencies were significantly different between low- and high-frequency STN-DBS. Patients showed a decrease in these verbal fluencies for high-frequency STN-DBS. Conclusion. Low-frequency STN-DBS may be less harmful to the verbal fluency of PD patients.

  18. The effects of subthalamic nucleus deep brain stimulation on parkinsonian tremor.

    PubMed

    Diamond, Alan; Shahed, Joohi; Jankovic, Joseph

    2007-09-15

    Deep brain stimulation (DBS) of the ventral intermediate (Vim) nucleus of the thalamus has been the target of choice for patients with disabling essential tremor or medication refractory parkinsonian tremor. Recently there is evidence that the subthalamic nucleus (STN) should be the targets for patients with tremor associated with Parkinson's disease (PD). To assess the effects of STN DBS on parkinsonian tremor, eight consecutive patients with PD and disabling tremor were videotaped using a standardized tremor protocol. Evaluations were performed at least 12 h after last dose of medication with the DBS turned off followed by optimal DBS on state. A rater blinded to DBS status evaluated randomized video segments with the tremor components of the Unified Parkinson Disease Rating Scale (UPDRS) and Tremor Rating Scale (TRS). Compared with DBS off state there were significant improvements in mean UPDRS tremor score 79.4% (p=0.008), total TRS score 69.9% (p=0.008) and upper extremity 92.5% (p=0.008) TRS subscore. Functional improvement was noted with pouring liquids. Our findings provide support that STN DBS is an effective treatment of tremor associated with PD.

  19. Effects of subthalamic deep brain stimulation on blink abnormalities of 6-OHDA lesioned rats.

    PubMed

    Kaminer, Jaime; Thakur, Pratibha; Evinger, Craig

    2015-05-01

    Parkinson's disease (PD) patients and the 6-hydroxydopamine (6-OHDA) lesioned rat model share blink abnormalities. In view of the evolutionarily conserved organization of blinking, characterization of blink reflex circuits in rodents may elucidate the neural mechanisms of PD reflex abnormalities. We examine the extent of this shared pattern of blink abnormalities by measuring blink reflex excitability, blink reflex plasticity, and spontaneous blinking in 6-OHDA lesioned rats. We also investigate whether 130-Hz subthalamic nucleus deep brain stimulation (STN DBS) affects blink abnormalities, as it does in PD patients. Like PD patients, 6-OHDA-lesioned rats exhibit reflex blink hyperexcitability, impaired blink plasticity, and a reduced spontaneous blink rate. At 130 Hz, but not 16 Hz, STN DBS eliminates reflex blink hyperexcitability and restores both short- and long-term blink plasticity. Replicating its lack of effect in PD patients, 130-Hz STN DBS does not reinstate a normal temporal pattern or rate to spontaneous blinking in 6-OHDA lesioned rats. These data show that the 6-OHDA lesioned rat is an ideal model system for investigating the neural bases of reflex abnormalities in PD and highlight the complexity of PD's effects on motor control, by showing that dopamine depletion does not affect all blink systems via the same neural mechanisms. Copyright © 2015 the American Physiological Society.

  20. Deep Brain Stimulation Frequency of the Subthalamic Nucleus Affects Phonemic and Action Fluency in Parkinson's Disease

    PubMed Central

    da Cruz, Aline Nunes; Beber, Bárbara Costa

    2016-01-01

    Introduction. Deep brain stimulation of the subthalamic nucleus (STN-DBS) in Parkinson's disease (PD) has been linked to a decline in verbal fluency. The decline can be attributed to surgical effects, but the relative contributions of the stimulation parameters are not well understood. This study aimed to investigate the impact of the frequency of STN-DBS on the performance of verbal fluency tasks in patients with PD. Methods. Twenty individuals with PD who received bilateral STN-DBS were evaluated. Their performances of verbal fluency tasks (semantic, phonemic, action, and unconstrained fluencies) upon receiving low-frequency (60 Hz) and high-frequency (130 Hz) STN-DBS were assessed. Results. The performances of phonemic and action fluencies were significantly different between low- and high-frequency STN-DBS. Patients showed a decrease in these verbal fluencies for high-frequency STN-DBS. Conclusion. Low-frequency STN-DBS may be less harmful to the verbal fluency of PD patients. PMID:28050309

  1. Subthalamic nucleus deep brain stimulation changes velopharyngeal control in Parkinson’s disease

    PubMed Central

    Hammer, Michael J.; Barlow, Steven M.; Lyons, Kelly E.; Pahwa, Rajesh

    2010-01-01

    Purpose Adequate velopharyngeal control is essential for speech, but may be impaired in Parkinson’s disease (PD). Bilateral subthalamic nucleus deep brain stimulation (STN DBS) improves limb function in PD, but the effects on velopharyngeal control remain unknown. We tested whether STN DBS would change aerodynamic measures of velopharyngeal control, and whether these changes were correlated with limb function and stimulation settings. Methods Seventeen PD participants with bilateral STN DBS were tested within a morning session after a minimum of 12 h since their most recent dose of anti-PD medication. Testing occurred when STN DBS was on, and again 1 h after STN DBS was turned off, and included aerodynamic measures during syllable production, and standard neurological ratings of limb function. Results We found that PD participants exhibited changes with STN DBS, primarily consistent with increased intraoral pressure (n = 7) and increased velopharyngeal closure (n = 5). These changes were modestly correlated with measures of limb function, and were correlated with stimulation frequency. Conclusion Our findings suggest that STN DBS may change velopharyngeal control during syllable production in PD, with greater benefit associated with low frequency stimulation. However, DBS demonstrates a more subtle influence on speech-related velopharyngeal control than limb motor control. This distinction and its underlying mechanisms are important to consider when assessing the impact of STN DBS on PD. PMID:20708741

  2. Subthalamic nucleus deep brain stimulation changes speech respiratory and laryngeal control in Parkinson's disease

    PubMed Central

    Barlow, Steven M.; Lyons, Kelly E.; Pahwa, Rajesh

    2010-01-01

    Adequate respiratory and laryngeal motor control are essential for speech, but may be impaired in Parkinson's disease (PD). Bilateral subthalamic nucleus deep brain stimulation (STN DBS) improves limb function in PD, but the effects on respiratory and laryngeal control remain unknown. We tested whether STN DBS would change aerodynamic measures of respiratory and laryngeal control, and whether these changes were correlated with limb function and stimulation parameters. Eighteen PD participants with bilateral STN DBS were tested within a morning session after a minimum of 12 h since their most recent dose of anti-PD medication. Testing occurred when DBS was on, and again 1 h after DBS was turned off, and included aerodynamic measures during syllable production, and standard clinical ratings of limb function. We found that PD participants exhibited changes with DBS, consistent with increased respiratory driving pressure (n = 9) and increased vocal fold closure (n = 9). However, most participants exceeded a typical operating range for these respiratory and laryngeal control variables with DBS. Changes were uncorrelated with limb function, but showed some correlation with stimulation frequency and pulse width, suggesting that speech may benefit more from low-frequency stimulation and shorter pulse width. Therefore, high-frequency STN DBS may be less beneficial for speech-related respiratory and laryngeal control than for limb motor control. It is important to consider these distinctions and their underlying mechanisms when assessing the impact of STN DBS on PD. PMID:20582431

  3. Changes in Vowel Articulation with Subthalamic Nucleus Deep Brain Stimulation in Dysarthric Speakers with Parkinson's Disease

    PubMed Central

    Langlois, Mélanie; Prud'Homme, Michel; Cantin, Léo

    2014-01-01

    Purpose. To investigate changes in vowel articulation with the electrical deep brain stimulation (DBS) of the subthalamic nucleus (STN) in dysarthric speakers with Parkinson's disease (PD). Methods. Eight Quebec-French speakers diagnosed with idiopathic PD who had undergone STN DBS were evaluated ON-stimulation and OFF-stimulation (1 hour after DBS was turned off). Vowel articulation was compared ON-simulation versus OFF-stimulation using acoustic vowel space and formant centralization ratio, calculated with the first (F1) and second formant (F2) of the vowels /i/, /u/, and /a/. The impact of the preceding consonant context on articulation, which represents a measure of coarticulation, was also analyzed as a function of the stimulation state. Results. Maximum vowel articulation increased during ON-stimulation. Analyses also indicate that vowel articulation was modulated by the consonant context but this relationship did not change with STN DBS. Conclusions. Results suggest that STN DBS may improve articulation in dysarthric speakers with PD, in terms of range of movement. Optimization of the electrical parameters for each patient is important and may lead to improvement in speech fine motor control. However, the impact on overall speech intelligibility may still be small. Clinical considerations are discussed and new research avenues are suggested. PMID:25400977

  4. Deep brain stimulation of the subthalamic nucleus: All that glitters isn't gold?

    PubMed

    Galati, Salvatore; Stefani, Alessandro

    2015-04-15

    With the silver anniversary of deep brain stimulation (DBS) behind us, this would seem to be a good juncture to consider its successes and unanswered questions. Bilateral subthalamic nucleus (STN) stimulation has changed the clinical perspective of several thousand Parkinson's disease (PD) patients worldwide. A recent reappraisal animates the field with strong arguments in favor of an anticipation of the stereotactic approach in patients with as little as 5 to 6 years of disease history if they manifest motor complications. From what was once a no-choice option, STN-DBS is now becoming more and more attractive to neurologists dealing with movement disorders. Despite the development of new pharmacological treatment and renewed rehabilitation programs able to modify the severity of drug-related complications, a resurgence of stimulation therapy reminiscent of an old era of medicine with an attendant blinkered mindset has emerged. Yet, the DBS-mediated effects are modest on critical aspects such as gait impairment and extremely variable depending on the clinical phenotype and individual clinical profile. Hence, the indication for DBS should become more, and not less, individually tailored. Those physicians considering deep brain stimulation (DBS) as a therapeutic option need to evaluate results beyond short-term quality of life, giving the correct weight to the direct and indirect costs over the longer term as well as to life prognosis. Unequivocal recourse to early-stimulation surgery necessitates investigations not limited to a mere comparative assessment versus drug-mediated benefits, but instead showing evidence of a clear degree of disease-modifying effect or a rescue of basal ganglia plasticity.

  5. No Effect of Subthalamic Deep Brain Stimulation on Intertemporal Decision-Making in Parkinson Patients123

    PubMed Central

    Wojtecki, Lars; Storzer, Lena; Schnitzler, Alfons

    2016-01-01

    Abstract Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a widely used treatment for the motor symptoms of Parkinson’s disease (PD). DBS or pharmacological treatment is believed to modulate the tendency to, or reverse, impulse control disorders. Several brain areas involved in impulsivity and reward valuation, such as the prefrontal cortex and striatum, are linked to the STN, and activity in these areas might be affected by STN-DBS. To investigate the effect of STN-DBS on one type of impulsive decision-making—delay discounting (i.e., the devaluation of reward with increasing delay until its receipt)—we tested 40 human PD patients receiving STN-DBS treatment and medication for at least 3 months. Patients were pseudo-randomly assigned to one of four groups to test the effects of DBS on/off states as well as medication on/off states on delay discounting. The delay-discounting task consisted of a series of choices among a smaller. sooner or a larger, later monetary reward. Despite considerable effects of DBS on motor performance, patients receiving STN-DBS did not choose more or less impulsively compared with those in the off-DBS group, as well as when controlling for risk attitude. Although null results have to be interpreted with caution, our findings are of significance to other researchers studying the effects of PD treatment on impulsive decision-making, and they are of clinical relevance for determining the therapeutic benefits of using STN-DBS. PMID:27257622

  6. Subthalamic nucleus deep brain stimulation impacts language in early Parkinson's disease.

    PubMed

    Phillips, Lara; Litcofsky, Kaitlyn A; Pelster, Michael; Gelfand, Matthew; Ullman, Michael T; Charles, P David

    2012-01-01

    Although deep brain stimulation (DBS) of the basal ganglia improves motor outcomes in Parkinson's disease (PD), its effects on cognition, including language, remain unclear. This study examined the impact of subthalamic nucleus (STN) DBS on two fundamental capacities of language, grammatical and lexical functions. These functions were tested with the production of regular and irregular past-tenses, which contrast aspects of grammatical (regulars) and lexical (irregulars) processing while controlling for multiple potentially confounding factors. Aspects of the motor system were tested by contrasting the naming of manipulated (motor) and non-manipulated (non-motor) objects. Performance was compared between healthy controls and early-stage PD patients treated with either DBS/medications or medications alone. Patients were assessed on and off treatment, with controls following a parallel testing schedule. STN-DBS improved naming of manipulated (motor) but not non-manipulated (non-motor) objects, as compared to both controls and patients with just medications, who did not differ from each other across assessment sessions. In contrast, STN-DBS led to worse performance at regulars (grammar) but not irregulars (lexicon), as compared to the other two subject groups, who again did not differ. The results suggest that STN-DBS negatively impacts language in early PD, but may be specific in depressing aspects of grammatical and not lexical processing. The finding that STN-DBS affects both motor and grammar (but not lexical) functions strengthens the view that both depend on basal ganglia circuitry, although the mechanisms for its differential impact on the two (improved motor, impaired grammar) remain to be elucidated.

  7. Subthalamic Nucleus Deep Brain Stimulation Impacts Language in Early Parkinson's Disease

    PubMed Central

    Phillips, Lara; Litcofsky, Kaitlyn A.; Pelster, Michael; Gelfand, Matthew

    2012-01-01

    Although deep brain stimulation (DBS) of the basal ganglia improves motor outcomes in Parkinson's disease (PD), its effects on cognition, including language, remain unclear. This study examined the impact of subthalamic nucleus (STN) DBS on two fundamental capacities of language, grammatical and lexical functions. These functions were tested with the production of regular and irregular past-tenses, which contrast aspects of grammatical (regulars) and lexical (irregulars) processing while controlling for multiple potentially confounding factors. Aspects of the motor system were tested by contrasting the naming of manipulated (motor) and non-manipulated (non-motor) objects. Performance was compared between healthy controls and early-stage PD patients treated with either DBS/medications or medications alone. Patients were assessed on and off treatment, with controls following a parallel testing schedule. STN-DBS improved naming of manipulated (motor) but not non-manipulated (non-motor) objects, as compared to both controls and patients with just medications, who did not differ from each other across assessment sessions. In contrast, STN-DBS led to worse performance at regulars (grammar) but not irregulars (lexicon), as compared to the other two subject groups, who again did not differ. The results suggest that STN-DBS negatively impacts language in early PD, but may be specific in depressing aspects of grammatical and not lexical processing. The finding that STN-DBS affects both motor and grammar (but not lexical) functions strengthens the view that both depend on basal ganglia circuitry, although the mechanisms for its differential impact on the two (improved motor, impaired grammar) remain to be elucidated. PMID:22880117

  8. Pyramidal tract activation due to subthalamic deep brain stimulation in Parkinson's disease.

    PubMed

    Mahlknecht, Philipp; Akram, Harith; Georgiev, Dejan; Tripoliti, Elina; Candelario, Joseph; Zacharia, Andre; Zrinzo, Ludvic; Hyam, Jonathan; Hariz, Marwan; Foltynie, Thomas; Rothwell, John C; Limousin, Patricia

    2017-08-01

    Subthalamic deep brain stimulation (STN-DBS) is an effective treatment for Parkinson's disease (PD), but can have side effects caused by stimulus spread to structures outside the target volume such as the pyramidal tract. To assess the relevance of pyramidal tract activation with STN-DBS in PD. In a multimodal, blinded study in 20 STN-DBS patients, we measured stimulation thresholds for evoking electromyographic activity in orbicularis oris and first dorsal interosseous muscles at each of 150 electrode sites. We also modeled the electric field spread and calculated its overlap with the estimated anatomical location of corticospinal and corticobulbar tracts from primary motor cortex using 3 Tesla MRI probabilistic tractography. Mean resting motor thresholds were significantly lower for the contralateral orbicularis oris (3.5 ± 1.0 mA) compared with ipsilaterally (4.1 ± 1.1 mA) and with the contralateral first dorsal interosseous (4.0 ± 1.2 mA). The modeled volumes of corticobulbar and corticospinal tract activated correlated inversely with the resting motor threshold of the contralateral orbicularis oris and first dorsal interosseous, respectively. Active motor thresholds were significantly lower compared with resting motor thresholds by around 30% to 35% and correlated with the clinically used stimulation amplitude. Backward multiple regression in 12 individuals with a "lateral-type" speech showed that stimulation amplitude, levodopa equivalent dose reduction postsurgery, preoperative speech intelligibility, and first dorsal interosseous resting motor thresholds explained 79.9% of the variance in postoperative speech intelligibility. Direct pyramidal tract activation can occur at stimulation thresholds that are within the range used in clinical routine. This spread of current compromises increase in stimulation strengths and is related to the development of side effects such as speech disturbances with chronic stimulation. © 2017 International

  9. Distinct phenotypes of speech and voice disorders in Parkinson's disease after subthalamic nucleus deep brain stimulation.

    PubMed

    Tsuboi, Takashi; Watanabe, Hirohisa; Tanaka, Yasuhiro; Ohdake, Reiko; Yoneyama, Noritaka; Hara, Kazuhiro; Nakamura, Ryoichi; Watanabe, Hazuki; Senda, Jo; Atsuta, Naoki; Ito, Mizuki; Hirayama, Masaaki; Yamamoto, Masahiko; Fujimoto, Yasushi; Kajita, Yasukazu; Wakabayashi, Toshihiko; Sobue, Gen

    2015-08-01

    To elucidate the phenotypes and pathophysiology of speech and voice disorders in Parkinson's disease (PD) with subthalamic nucleus deep brain stimulation (STN-DBS). We conducted a cross-sectional study on 76 PD patients treated with bilateral STN-DBS (PD-DBS) and 33 medically treated PD patients (PD-Med). Speech and voice functions, electrode positions, motor function and cognitive function were comprehensively assessed. Moreover, speech and voice functions were compared between the on-stimulation and off-stimulation conditions in 42 PD-DBS patients. Speech and voice disorders in PD-DBS patients were significantly worse than those in PD-Med patients. Factor analysis and subsequent cluster analysis classified PD-DBS patients into five clusters: relatively good speech and voice function type, 25%; stuttering type, 24%; breathy voice type, 16%; strained voice type, 18%; and spastic dysarthria type, 17%. STN-DBS ameliorated voice tremor or low volume; however, it deteriorated the overall speech intelligibility in most patients. Breathy voice did not show significant changes and stuttering exhibited slight improvement after stopping stimulation. In contrast, patients with strained voice type or spastic dysarthria type showed a greater improvement after stopping stimulation. Spastic dysarthria type patients showed speech disorders similar to spastic dysarthria, which is associated with bilateral upper motor neuron involvement. Strained voice type and spastic dysarthria type appeared to be related to current diffusion to the corticobulbar fibres. Stuttering and breathy voice can be aggravated by STN-DBS, but are mainly due to aging or PD itself. Strained voice and spastic dysarthria are considered corticobulbar side effects. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  10. Patients' expectations in subthalamic nucleus deep brain stimulation surgery for Parkinson disease.

    PubMed

    Hasegawa, Harutomo; Samuel, Michael; Douiri, Abdel; Ashkan, Keyoumars

    2014-12-01

    Subthalamic nucleus (STN) deep brain stimulation (DBS) is an established treatment for patients with advanced Parkinson disease. However, some patients feel less satisfied with the outcome of surgery. We sought to study the relationship between expectations, satisfaction, and outcome in STN DBS for Parkinson disease. Twenty-two consecutive patients undergoing STN DBS completed a modified 39-item Parkinson disease questionnaire (PDQ-39) preoperatively and 6 months postoperatively. A satisfaction questionnaire accompanied the postoperative questionnaire. Patients expected a significant improvement from surgery preoperatively: preoperative score (median PDQ-39 summary score [interquartile range]): 37.0 (9.5), expected postoperative score: 13.0 (8.0), P < 0.001. Patients improved after surgery (preoperative score 39.0 [11.5], postoperative score 25.0 [14.3], P = 0.003), although there was a substantial disparity between the expected change (24.0 [15.0]) and actual change (14.0 [22.5]), P = 0.008. However, most patients felt that surgery fulfilled their expectations (mean score on a 0%-100% visual analog scale); (75.3 ± 17.8) and were satisfied (73.3 ± 25.3). Satisfaction correlated with fulfillment of expectations (r = 0.910, P < 0.001) but not with quantitative changes in PDQ-39 scores. Addressing patients' expectations both preoperatively and postoperatively may play an important role in patient satisfaction, and therefore overall success, of STN DBS surgery for Parkinson disease. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Reduced GABA Content in the Motor Thalamus during Effective Deep Brain Stimulation of the Subthalamic Nucleus

    PubMed Central

    Stefani, Alessandro; Fedele, Ernesto; Pierantozzi, Mariangela; Galati, Salvatore; Marzetti, Francesco; Peppe, Antonella; Pastore, Francesco Saverio; Bernardi, Giorgio; Stanzione, Paolo

    2011-01-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN), in Parkinson's disease (PD) patients, is a well established therapeutic option, but its mechanisms of action are only partially known. In our previous study, the clinical transitions from OFF- to ON-state were not correlated with significant changes of GABA content inside GPi or substantia nigra reticulata. Here, biochemical effects of STN-DBS have been assessed in putamen (PUT), internal pallidus (GPi), and inside the antero-ventral thalamus (VA), the key station receiving pallidothalamic fibers. In 10 advanced PD patients undergoing surgery, microdialysis samples were collected before and during STN-DBS. cGMP, an index of glutamatergic transmission, was measured in GPi and PUT by radioimmunoassay, whereas GABA from VA was measured by HPLC. During clinically effective STN-DBS, we found a significant decrease in GABA extracellular concentrations in VA (−30%). Simultaneously, cGMP extracellular concentrations were enhanced in PUT (+200%) and GPi (+481%). These findings support a thalamic dis-inhibition, in turn re-establishing a more physiological corticostriatal transmission, as the source of motor improvement. They indirectly confirm the relevance of patterning (instead of mere changes of excitability) and suggest that a rigid interpretation of the standard model, at least when it indicates the hyperactive indirect pathway as key feature of hypokinetic signs, is unlikely to be correct. Finally, given the demonstration of a key role of VA in inducing clinical relief, locally administration of drugs modulating GABA transmission in thalamic nuclei could become an innovative therapeutic strategy. PMID:21519387

  12. Low-frequency subthalamic nucleus deep brain stimulation for axial symptoms in advanced Parkinson's disease.

    PubMed

    Sidiropoulos, Christos; Walsh, Richard; Meaney, Christopher; Poon, Y Y; Fallis, Melanie; Moro, Elena

    2013-09-01

    Axial symptoms such as freezing of gait and falls are common manifestations of advanced Parkinson's disease (PD) and are partially responsive to medical treatment. High-frequency (≥130 Hz) deep brain stimulation (DBS) of the subthalamic nucleus (STN) is highly efficacious in ameliorating appendicular symptoms in PD. However, it is typically less effective in improving axial symptomatology, especially in the long term. We have studied the effects of low-frequency stimulation (LFS) (≤80 Hz) for improving speech, gait and balance dysfunction in the largest patient population to date. PD patients with bilateral STN-DBS and resistant axial symptoms were switched from chronic 130 Hz stimulation to LFS and followed up to 4 years. Primary outcome measures were total motor UPDRS scores, and axial and gait subscores before and after LFS. Bivariate analyses and correlation coefficients were calculated for the different conditions. Potential predictors of therapeutic response were also investigated. Forty-five advanced PD patients who had high frequency stimulation (HFS) for 39.5 ± 27.8 consecutive months were switched to LFS. LFS was kept on for a median period of 111.5 days before the assessment. There was no significant improvement in any of the primary outcomes between HFS and LFS, although a minority of patients preferred to be maintained on LFS for longer periods of time. No predictive factors of response could be identified. There was overall no improvement from LFS in axial symptoms. This could be partly due to some study limitations. Larger prospective trials are warranted to better clarify the impact of stimulation frequency on axial signs.

  13. Improved sequence learning with subthalamic nucleus deep brain stimulation: evidence for treatment-specific network modulation.

    PubMed

    Mure, Hideo; Tang, Chris C; Argyelan, Miklos; Ghilardi, Maria-Felice; Kaplitt, Michael G; Dhawan, Vijay; Eidelberg, David

    2012-02-22

    We used a network approach to study the effects of anti-parkinsonian treatment on motor sequence learning in humans. Eight Parkinson's disease (PD) patients with bilateral subthalamic nucleus (STN) deep brain stimulation underwent H(2)(15)O positron emission tomography (PET) imaging to measure regional cerebral blood flow (rCBF) while they performed kinematically matched sequence learning and movement tasks at baseline and during stimulation. Network analysis revealed a significant learning-related spatial covariance pattern characterized by consistent increases in subject expression during stimulation (p = 0.008, permutation test). The network was associated with increased activity in the lateral cerebellum, dorsal premotor cortex, and parahippocampal gyrus, with covarying reductions in the supplementary motor area (SMA) and orbitofrontal cortex. Stimulation-mediated increases in network activity correlated with concurrent improvement in learning performance (p < 0.02). To determine whether similar changes occurred during dopaminergic pharmacotherapy, we studied the subjects during an intravenous levodopa infusion titrated to achieve a motor response equivalent to stimulation. Despite consistent improvement in motor ratings during infusion, levodopa did not alter learning performance or network activity. Analysis of learning-related rCBF in network regions revealed improvement in baseline abnormalities with STN stimulation but not levodopa. These effects were most pronounced in the SMA. In this region, a consistent rCBF response to stimulation was observed across subjects and trials (p = 0.01), although the levodopa response was not significant. These findings link the cognitive treatment response in PD to changes in the activity of a specific cerebello-premotor cortical network. Selective modulation of overactive SMA-STN projection pathways may underlie the improvement in learning found with stimulation.

  14. Deep brain stimulation of the subthalamic nucleus increases premature responding in a rat gambling task.

    PubMed

    Aleksandrova, Lily R; Creed, Meaghan C; Fletcher, Paul J; Lobo, Daniela S S; Hamani, Clement; Nobrega, José N

    2013-05-15

    Deep brain stimulation of the subthalamic nucleus (STN-DBS) is a treatment option for the motor symptoms of Parkinson's disease (PD). However, several recent studies have found an association between STN-DBS and increased impulsivity. Currently, it is not clear whether the observed increase in impulsivity results from STN-DBS per se, or whether it involves an interaction with the underlying PD neuropathology and/or intake of dopaminergic drugs. We investigated the effects of STN-DBS on performance of intact rats on two tasks measuring impulsive responding: a novel rat gambling task (rGT) and a differential reinforcement of low rate responding (DRL20s) schedule. Following initial behavioural training, animals received electrode implantation into the STN (n=24) or sham surgery (n=24), and were re-tested on their assigned behavioural task, with or without STN-DBS. Bilateral STN-DBS administered for two hours immediately prior to testing, had no effects on rGT choice behaviour or on DRL response inhibition (p>0.05). However, STN-DBS significantly increased premature responding in the rGT task (p=0.0004), an effect that took several sessions to develop and persisted in subsequent trials when no stimulation was given. Consistent with the notion of distinct facets of impulsivity with unique neurochemical underpinnings, we observed differential effects of STN-DBS in the two tasks employed. These results suggest that STN-DBS in the absence of parkinsonism may not lead to a general loss of inhibitory control, but may instead affect impulsivity under specific conditions.

  15. Subthalamic Nucleus Deep Brain Stimulation May Reduce Medication Costs in Early Stage Parkinson's Disease.

    PubMed

    Hacker, Mallory L; Currie, Amanda D; Molinari, Anna L; Turchan, Maxim; Millan, Sarah M; Heusinkveld, Lauren E; Roach, Jonathon; Konrad, Peter E; Davis, Thomas L; Neimat, Joseph S; Phibbs, Fenna T; Hedera, Peter; Byrne, Daniel W; Charles, David

    2016-01-01

    Subthalamic nucleus deep brain stimulation (STN-DBS) is well-known to reduce medication burden in advanced stage Parkinson's disease (PD). Preliminary data from a prospective, single blind, controlled pilot trial demonstrated that early stage PD subjects treated with STN-DBS also required less medication than those treated with optimal drug therapy (ODT). The purpose of this study was to analyze medication cost and utilization from the pilot trial of DBS in early stage PD and to project 10 year medication costs. Medication data collected at each visit were used to calculate medication costs. Medications were converted to levodopa equivalent daily dose, categorized by medication class, and compared. Medication costs were projected to advanced stage PD, the time when a typical patient may be offered DBS. Medication costs increased 72% in the ODT group and decreased 16% in the DBS+ODT group from baseline to 24 months. This cost difference translates into a cumulative savings for the DBS+ODT group of $7,150 over the study period. Projected medication cost savings over 10 years reach $64,590. Additionally, DBS+ODT subjects were 80% less likely to require polypharmacy compared with ODT subjects at 24 months (p <  0.05; OR = 0.2; 95% CI: 0.04-0.97). STN-DBS in early PD reduced medication cost over the two-year study period. DBS may offer substantial long-term reduction in medication cost by maintaining a simplified, low dose medication regimen. Further study is needed to confirm these findings, and the FDA has approved a pivotal, multicenter clinical trial evaluating STN-DBS in early PD.

  16. Interventional magnetic resonance imaging-guided subthalamic nucleus deep brain stimulation for Parkinson's disease: Patient selection.

    PubMed

    Azmi, Hooman; Gupta, Fiona; Vukic, Mario; Kreitner, Jason; Kera, Elizabeth; Nicola, Gregory; Pierce, Sean; Panush, David; Cohen, Randy

    2016-01-01

    Interventional magnetic resonance imaging (iMRI) guided deep brain stimulation (DBS) for Parkinson's disease (PD) has been shown to be effective. The costs of a dedicated intraoperative MRI may be prohibitive. The procedure can also be performed in a diagnostic scanner, however this presents challenges for utilization of time when the scanner is used both as a diagnostic and an interventional unit. This report outlines our novel methodology for patient selection for implantation in a diagnostic MR scanner, as an attempt to streamline the use of resources. A retrospective review of our outcomes is also presented. DBS candidacy evaluation included a PD questionnaire-39. Anxiety, age, difficulties in communication and body habitus were factors that were assessed in selecting patients for this technique. Eleven patients underwent iMRI-guided DBS implantation in the subthalamic nucleus. All patients were implanted bilaterally. Unified PD rating scale (UPDRS) part III and L-dopa dose were compared pre- and post-stimulation. A cohort of 11 DBS patients not selected for iMRI-guided DBS were also reported for comparison. For the iMRI-guided patients, mean "Off" UPDRS III score was 47.6 (standard deviation [SD] 8.26). Postoperative "On" medication, "On" stimulation UPDRS III was 13.6 (SD 5.23). Mean preoperative L-dopa dose was 1060 mg (SD 474.3) and mean postoperative L-dopa dose was 320 (SD 298.3). iMRI-guided DBS is a newly emerging technique for surgical treatment of patients with PD. We present a novel scoring system for patient selection assessing anxiety, age, ability to communicate, and body habitus to identify patients who will be benefited most from this technique.

  17. Stop! border ahead: Automatic detection of subthalamic exit during deep brain stimulation surgery.

    PubMed

    Valsky, Dan; Marmor-Levin, Odeya; Deffains, Marc; Eitan, Renana; Blackwell, Kim T; Bergman, Hagai; Israel, Zvi

    2017-01-01

    Microelectrode recordings along preplanned trajectories are often used for accurate definition of the subthalamic nucleus (STN) borders during deep brain stimulation (DBS) surgery for Parkinson's disease. Usually, the demarcation of the STN borders is performed manually by a neurophysiologist. The exact detection of the borders is difficult, especially detecting the transition between the STN and the substantia nigra pars reticulata. Consequently, demarcation may be inaccurate, leading to suboptimal location of the DBS lead and inadequate clinical outcomes. We present machine-learning classification procedures that use microelectrode recording power spectra and allow for real-time, high-accuracy discrimination between the STN and substantia nigra pars reticulata. A support vector machine procedure was tested on microelectrode recordings from 58 trajectories that included both STN and substantia nigra pars reticulata that achieved a 97.6% consistency with human expert classification (evaluated by 10-fold cross-validation). We used the same data set as a training set to find the optimal parameters for a hidden Markov model using both microelectrode recording features and trajectory history to enable real-time classification of the ventral STN border (STN exit). Seventy-three additional trajectories were used to test the reliability of the learned statistical model in identifying the exit from the STN. The hidden Markov model procedure identified the STN exit with an error of 0.04 ± 0.18 mm and detection reliability (error < 1 mm) of 94%. The results indicate that robust, accurate, and automatic real-time electrophysiological detection of the ventral STN border is feasible. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

  18. Improved Sequence Learning with Subthalamic Nucleus Deep Brain Stimulation: Evidence for Treatment-Specific Network Modulation

    PubMed Central

    Mure, Hideo; Tang, Chris C.; Argyelan, Miklos; Ghilardi, Maria-Felice; Kaplitt, Michael G.; Dhawan, Vijay; Eidelberg, David

    2015-01-01

    We used a network approach to study the effects of anti-parkinsonian treatment on motor sequence learning in humans. Eight Parkinson’s disease (PD) patients with bilateral subthalamic nucleus (STN) deep brain stimulation underwent H2 15Opositron emission tomography (PET) imaging to measure regional cerebral blood flow (rCBF) while they performed kinematically matched sequence learning and movement tasks at baseline and during stimulation. Network analysis revealed a significant learning-related spatial covariance pattern characterized by consistent increases in subject expression during stimulation (p = 0.008, permutation test). The network was associated with increased activity in the lateral cerebellum, dorsal premotor cortex, and parahippocampal gyrus, with covarying reductions in the supplementary motor area (SMA) and orbitofrontal cortex. Stimulation-mediated increases in network activity correlated with concurrent improvement in learning performance (p < 0.02). To determine whether similar changes occurred during dopaminergic pharmacotherapy, we studied the subjects during an intravenous levodopa infusion titrated to achieve a motor response equivalent to stimulation. Despite consistent improvement in motor ratings during infusion, levodopa did not alter learning performance or network activity. Analysis of learning-related rCBF in network regions revealed improvement in baseline abnormalities with STN stimulation but not levodopa. These effects were most pronounced in the SMA. In this region, a consistent rCBF response to stimulation was observed across subjects and trials (p = 0.01), although the levodopa response was not significant. These findings link the cognitive treatment response in PD to changes in the activity of a specific cerebello-premotor cortical network. Selective modulation of overactive SMA–STN projection pathways may underlie the improvement in learning found with stimulation. PMID:22357863

  19. Early versus delayed bilateral subthalamic deep brain stimulation for parkinson's disease: a decision analysis.

    PubMed

    Espay, Alberto J; Vaughan, Jennifer E; Marras, Connie; Fowler, Rob; Eckman, Mark H

    2010-07-30

    The long-term benefits of subthalamic nucleus deep brain stimulation (STN DBS) applied earlier in the disease course, before significant disability accumulates, remain to be determined. We developed a Markov state transition decision analytic model to compare effectiveness in quality-adjusted life years (QALYs) of STN DBS applied to patients with PD at an "early" ("off time" 10-20%) versus "delayed" stage ("off time" >40%). A lifelong time horizon and societal perspective were assumed. Probabilities and rates were obtained from literature review; utilities were derived using the time trade-off technique and a computer-assisted utility assessment software tool applied to a cohort of 22 STN-DBS and 21 non-STN-DBS PD patients. Uncertainty was assessed through one- and two-way sensitivity analyses and probabilistic sensitivity analysis using second-order Monte Carlo simulations. Early STN DBS was preferred with a quality-adjusted life expectancy of 22.3 QALYs, a gain of 2.5 QALYs over those with delayed surgery (19.8 QALYs). Early STN DBS was preferred in 69% of 5,000 Monte Carlo simulations. Early surgery was robustly favored through most sensitivity analyses. Delayed STN DBS afforded greater QALYs when using utility estimates exclusively from non-STN-DBS patients and, for the entire group, if the rate of motor progression were to exceed 25% per year. Although decision modeling requires assumptions and simplifications, our exploratory analysis suggests that STN DBS performed in early PD may convey greater quality-adjusted life expectancy when compared to a delayed procedure. These findings support further evaluation of early STN DBS in a controlled clinical trial. (c) 2010 Movement Disorder Society.

  20. Camptocormia and deep brain stimulation: The interesting overlapping etiologies and the therapeutic role of subthalamic nucleus-deep brain stimulation in Parkinson disease with camptocormia.

    PubMed

    Ekmekci, Hakan; Kaptan, Hulagu

    2016-01-01

    Camptocormia is known as "bent spine syndrome" and defined as a forward hyperflexion. The most common etiologic factor is related with the movement disorders, mainly in Parkinson's disease (PD). We present the case of a 51-year-old woman who has been followed with PD for the last 10 years, and also under the therapy for PD. An unappreciated correlation low back pain with camptocormia developed. She underwent deep brain stimulation (DBS) in the subthalamic nucleus bilaterally and improved her bending posture. The relationship between the DBS and camptocormia is discussed in this unique condition.

  1. Camptocormia and deep brain stimulation: The interesting overlapping etiologies and the therapeutic role of subthalamic nucleus-deep brain stimulation in Parkinson disease with camptocormia

    PubMed Central

    Ekmekci, Hakan; Kaptan, Hulagu

    2016-01-01

    Background: Camptocormia is known as “bent spine syndrome” and defined as a forward hyperflexion. The most common etiologic factor is related with the movement disorders, mainly in Parkinson's disease (PD). Case Description: We present the case of a 51-year-old woman who has been followed with PD for the last 10 years, and also under the therapy for PD. An unappreciated correlation low back pain with camptocormia developed. She underwent deep brain stimulation (DBS) in the subthalamic nucleus bilaterally and improved her bending posture. Conclusion: The relationship between the DBS and camptocormia is discussed in this unique condition. PMID:26958425

  2. Deep brain stimulation of the subthalamic nucleus in Parkinson's disease: From history to the interaction with the monoaminergic systems.

    PubMed

    Faggiani, E; Benazzouz, A

    2017-04-01

    Parkinson's disease is the second most common neurodegenerative disorder, characterized by the manifestation of motor symptoms, which are mainly attributed to the degeneration of dopamine neurons in the pars compacta of substantia nigra. Based on advancements in the understanding of the pathophysiology of the disease, especially in animal models, the subthalamic nucleus has been pointed as a major target for deep brain stimulation in the treatment of motor symptoms, first developed in non-human primate and then successfully transfered to parkinsonian patients. Nevertheless, despite the focus on motor deficits, Parkinson's disease is also characterized by the manifestation of non-motor symptoms, which can be due to the additional degeneration of norepinephrine, serotonin and cholinergic systems. The pathophysiology of the non-motor symptoms is under studied and consequently not well treated. Furthermore, data from the literature about the impact of subthalamic deep brain stimulation on non-motor disorders are controversial and still under debate. Similarly, the risk of mood disorders post-deep brain stimulation surgery remains also controversial. Here, we review the clinical and experimental data of this neurosurgical approach on motor and non-motor behaviors and provide evidence for its interaction with the monoaminergic systems.

  3. Capgras Syndrome in a Patient with Parkinson's Disease after Bilateral Subthalamic Nucleus Deep Brain Stimulation: A Case Report

    PubMed Central

    Kyrtsos, Christina Rose; Stahl, Mark C.; Eslinger, Paul; Subramanian, Thyagarajan; Lucassen, Elisabeth B.

    2015-01-01

    Capgras syndrome is a delusional misidentification syndrome (DMS) which can be seen in neurodegenerative diseases such as Lewy body dementia and, to a lesser extent, in Parkinson's disease (PD). Here, we report the case of a 78-year-old man with a history of idiopathic PD who developed Capgras syndrome following bilateral subthalamic nucleus deep brain stimulation (DBS) implantation. As the risk of DMS has been related to deficits in executive, memory, and visuospatial function preoperatively, this case highlights the importance of continuing to improve patient selection for DBS surgery. Capgras syndrome is a rare potential complication of DBS surgery in PD patients with preexisting cognitive decline. PMID:26078747

  4. Verbal fluency in patients receiving bilateral versus left-sided deep brain stimulation of the subthalamic nucleus for Parkinson's disease.

    PubMed

    Sjöberg, Rickard L; Lidman, Elin; Häggström, Björn; Hariz, Marwan I; Linder, Jan; Fredricks, Anna; Blomstedt, Patric

    2012-05-01

    The purpose of this study was to investigate the relative effects of unilateral (left-sided) versus bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) on verbal fluency. To do this, 10 Parkinson's disease patients with predominantly bilateral motor symptoms who received bilateral STN DBS were compared with 6 patients suffering from predominantly unilateral symptoms who received STN DBS on the left side only. The results suggest that unilateral STN DBS of the speech dominant hemisphere is associated with significantly less declines in measures of verbal fluency as compared to bilateral stimulation.

  5. Impulse control behaviors and subthalamic deep brain stimulation in Parkinson disease.

    PubMed

    Merola, Aristide; Romagnolo, Alberto; Rizzi, Laura; Rizzone, Mario Giorgio; Zibetti, Maurizio; Lanotte, Michele; Mandybur, George; Duker, Andrew P; Espay, Alberto J; Lopiano, Leonardo

    2017-01-01

    To determine the clinical and demographic correlates of persistent, remitting, and new-onset impulse control behaviors (ICBs) before and after subthalamic deep brain stimulation (STN-DBS) in Parkinson's disease (PD). We compared the pre- and post-surgical prevalence of ICBs, classified as impulse control disorders (ICD), dopamine dysregulation syndrome (DDS), and punding in 150 consecutive PD STN-DBS-treated patients and determined the association with motor, cognitive, neuropsychological, and neuropsychiatric endpoints. At baseline (before STN-DBS), ICBs were associated with younger age (p = 0.045) and male gender (85 %; p = 0.001). Over an average follow-up of 4.3 ± 2.1 years of chronic STN-DBS there was an overall trend for reduction in ICBs (from 17.3 to 12.7 %; p = 0.095) with significant improvement in hypersexuality (12-8.0 %; p = 0.047), gambling (10.7-5.3 %; p = 0.033), and DDS (4.7-0 %; p < 0.001). ICB remitted in 18/26 patients (69 %) and persisted in 8/26 (31 %); the latter group was characterized by higher levodopa equivalent daily dose. Patients who developed a new-onset ICB during follow-up (n = 11/150) were characterized by younger age (p = 0.042), lower dyskinesia improvement (p ≤ 0.035), and a gender distribution with higher prevalence of women (p = 0.018). In addition, new-onset ICB was more common among patients with borderline, schizoid, and/or schizotypal traits of personality disorders; persistent ICB in those with obsessive-compulsive traits. PD-related ICBs exhibit a complex outcome after STN-DBS, with a tendency for overall reduction but with age, gender, dopaminergic therapy, and neuropsychiatric features exerting independent effects.

  6. Motor responses of muscles supplied by cranial nerves to subthalamic nucleus deep brain stimuli.

    PubMed

    Costa, João; Valls-Solé, Josep; Valldeoriola, Francesc; Rumià, Jordi; Tolosa, Eduardo

    2007-01-01

    The distribution of human corticobulbar motor excitatory and inhibitory output is not fully understood. In particular, it is unclear whether the pattern of innervation is the same for upper and lower facial muscles, and what is the motor cortical area giving rise to such innervation. We used electrodes implanted in the subthalamic nucleus (STN) in patients with Parkinson's disease to activate motor tracts at a subcortical level. We examined the excitatory and inhibitory effects of unilateral single STN deep brain stimulation (sSTN-DBS) in 14 patients by taking recordings from facial, cervical and upper limb muscles on both sides. We measured the latency and amplitude of the motor-evoked potentials (MEPs), and the latency and duration of the silent periods, and compared ipsilateral with contralateral responses and responses obtained in different muscles. Unilateral sSTN-DBS induced strictly contralateral MEPs in the trapezius, deltoid, biceps and thenar muscles. The same stimulus always induced bilateral MEPs in the orbicularis oculi, orbicularis oris, masseter and sternocleidomastoid at a mean latency in the range 6.0-9.1 ms. MEP latencies in the orbicularis oculi and orbicularis oris were significantly longer than in the masseter and sternocleidomastoid (P < 0.01). A short latency small action potential was recorded in the ipsilateral orbicularis oculi that was likely generated by activation of extraocular muscles. During sustained voluntary muscle contraction, a silent period was recorded at similar onset latency on both sides. This period was significantly shorter in orbicularis oculi than in masseter, and in the ipsilateral side for both muscles (P < 0.01). sSTN-DBS is able to activate the descending projecting fibres in the corticobulbar tract eliciting bilateral MEPs and silent periods in facial and cranial muscles. This suggests that fibres to both ipsi- and contralateral motor nuclei descend together at the level of the STN. These findings are relevant in

  7. Effects of Medication and Subthalamic Nucleus Deep Brain Stimulation on Tongue Movements in Speakers with Parkinson's Disease Using Electropalatography: A Pilot Study

    ERIC Educational Resources Information Center

    Hartinger, Mariam; Tripoliti, Elina; Hardcastle, William J.; Limousin, Patricia

    2011-01-01

    Parkinson's disease (PD) affects speech in the majority of patients. Subthalamic nucleus deep brain stimulation (STN-DBS) is particularly effective in reducing tremor and rigidity. However, its effect on speech is variable. The aim of this pilot study was to quantify the effects of bilateral STN-DBS and medication on articulation, using…

  8. Articulatory Closure Proficiency in Patients with Parkinson's Disease Following Deep Brain Stimulation of the Subthalamic Nucleus and Caudal Zona Incerta

    ERIC Educational Resources Information Center

    Karlsson, Fredrik; Olofsson, Katarina; Blomstedt, Patric; Linder, Jan; Nordh, Erik; van Doorn, Jan

    2014-01-01

    Purpose: The present study aimed at comparing the effects of deep brain stimulation (DBS) treatment of the subthalamic nucleus (STN) and the caudal zona incerta (cZi) on the proficiency in achieving oral closure and release during plosive production of people with Parkinson's disease. Method: Nineteen patients participated preoperatively and…

  9. Articulatory Closure Proficiency in Patients with Parkinson's Disease Following Deep Brain Stimulation of the Subthalamic Nucleus and Caudal Zona Incerta

    ERIC Educational Resources Information Center

    Karlsson, Fredrik; Olofsson, Katarina; Blomstedt, Patric; Linder, Jan; Nordh, Erik; van Doorn, Jan

    2014-01-01

    Purpose: The present study aimed at comparing the effects of deep brain stimulation (DBS) treatment of the subthalamic nucleus (STN) and the caudal zona incerta (cZi) on the proficiency in achieving oral closure and release during plosive production of people with Parkinson's disease. Method: Nineteen patients participated preoperatively and…

  10. Effects of Medication and Subthalamic Nucleus Deep Brain Stimulation on Tongue Movements in Speakers with Parkinson's Disease Using Electropalatography: A Pilot Study

    ERIC Educational Resources Information Center

    Hartinger, Mariam; Tripoliti, Elina; Hardcastle, William J.; Limousin, Patricia

    2011-01-01

    Parkinson's disease (PD) affects speech in the majority of patients. Subthalamic nucleus deep brain stimulation (STN-DBS) is particularly effective in reducing tremor and rigidity. However, its effect on speech is variable. The aim of this pilot study was to quantify the effects of bilateral STN-DBS and medication on articulation, using…

  11. Spatial distance between anatomically- and physiologically-identified targets in subthalamic nucleus deep brain stimulation in Parkinson's disease.

    PubMed

    Parvaresh-Rizi, Mansour; Tabibkhoei, Alireza; Shahidi, Gholamali; Vaidyanathan, Janardan; Tabibkhoei, Amirreza; Rohani, Mohammad

    2016-01-05

    Subthalamic nucleus (STN) stimulation is the treatment of choice for carefully chosen patients with idiopathic Parkinson's disease (PD) and refractory motor fluctuations. We evaluated the value of intraoperative electrophysiology during STN deep brain stimulation (DBS) procedures in refining the anatomically-defined target. We determined the spatial distance between the anatomical and physiological targets along x, y and z axes in 50 patients with PD who underwent bilateral subthalamic nucleus DBS surgery. The mean spatial distance between anatomical and functional targets was 1.84 ± 0.88 mm and the least distances in different methods were 0.66 mm [standard error (SE): 0.07], 1.07 mm (SE: 0.08) and 1.01 mm (SE: 0.08) on x, y and z axes, respectively, for the combined method. The most physiologically-accurate anatomical targeting was achieved via a combination of multiple independent methods. There was a statistically significant difference between the anatomical and functional targets in all methods (even the combined) on the y coordinate, emphasizing the need for intra-operative electrophysiological monitoring to refine the anatomico-radiologically-defined target.

  12. Spatial distance between anatomically- and physiologically-identified targets in subthalamic nucleus deep brain stimulation in Parkinson’s disease

    PubMed Central

    Parvaresh-Rizi, Mansour; Tabibkhoei, Alireza; Shahidi, Gholamali; Vaidyanathan, Janardan; Tabibkhoei, Amirreza; Rohani, Mohammad

    2016-01-01

    Background: Subthalamic nucleus (STN) stimulation is the treatment of choice for carefully chosen patients with idiopathic Parkinson's disease (PD) and refractory motor fluctuations. We evaluated the value of intraoperative electrophysiology during STN deep brain stimulation (DBS) procedures in refining the anatomically-defined target. Methods: We determined the spatial distance between the anatomical and physiological targets along x, y and z axes in 50 patients with PD who underwent bilateral subthalamic nucleus DBS surgery. Results: The mean spatial distance between anatomical and functional targets was 1.84 ± 0.88 mm and the least distances in different methods were 0.66 mm [standard error (SE): 0.07], 1.07 mm (SE: 0.08) and 1.01 mm (SE: 0.08) on x, y and z axes, respectively, for the combined method. Conclusion: The most physiologically-accurate anatomical targeting was achieved via a combination of multiple independent methods. There was a statistically significant difference between the anatomical and functional targets in all methods (even the combined) on the y coordinate, emphasizing the need for intra-operative electrophysiological monitoring to refine the anatomico-radiologically-defined target. PMID:27141275

  13. Older Candidates for Subthalamic Deep Brain Stimulation in Parkinson's Disease Have a Higher Incidence of Psychiatric Serious Adverse Events

    PubMed Central

    Cozac, Vitalii V.; Ehrensperger, Michael M.; Gschwandtner, Ute; Hatz, Florian; Meyer, Antonia; Monsch, Andreas U.; Schuepbach, Michael; Taub, Ethan; Fuhr, Peter

    2016-01-01

    Objective: To investigate the incidence of serious adverse events (SAE) of subthalamic deep brain stimulation (STN-DBS) in elderly patients with Parkinson's disease (PD). Methods: We investigated a group of 26 patients with PD who underwent STN-DBS at mean age 63.2 ± 3.3 years. The operated patients from the EARLYSTIM study (mean age 52.9 ± 6.6) were used as a comparison group. Incidences of SAE were compared between these groups. Results: A higher incidence of psychosis and hallucinations was found in these elderly patients compared to the younger patients in the EARLYSTIM study (p < 0.01). Conclusions: The higher incidence of STN-DBS-related psychiatric complications underscores the need for comprehensive psychiatric pre- and postoperative assessment in older DBS candidates. However, these psychiatric SAE were transient, and the benefits of DBS clearly outweighed its adverse effects. PMID:27375478

  14. Perceived articulatory precision in patients with Parkinson's disease after deep brain stimulation of subthalamic nucleus and caudal zona incerta.

    PubMed

    Eklund, Elisabeth; Qvist, Johanna; Sandström, Lena; Viklund, Fanny; Van Doorn, Jan; Karlsson, Fredrik

    2015-02-01

    The effect of deep brain stimulation (DBS) of the subthalamic nucleus (STN) and caudal zona incerta (cZi) on speech articulation in patients with Parkinson's disease (PD) was investigated. Read speech samples were collected from nine patients with STN-DBS and 10 with cZi-DBS. The recordings were made pre-operatively and 12 months post-operatively with stimulator on and off (on medication). Blinded, randomised, repeated perceptual assessments were performed on words and isolated fricatives extracted from the recordings to assess (1) overall articulatory quality ratings, (2) frequency of occurrence of misarticulation patterns and (3) fricative production. Statistically significant worsening of articulatory measures on- compared with off-stimulation occurred in the cZi-DBS group, with deteriorated articulatory precision ratings, increased presence of misarticulations (predominately altered realisations of plosives and fricatives) and a reduced accuracy in fricative production. A similar, but not significant, trend was found for the STN-DBS group.

  15. The influence of bilateral subthalamic nucleus deep brain stimulation on impulsivity and prepulse inhibition in Parkinson’s disease patients

    PubMed Central

    Gee, Lucy; Smith, Heather; Cruz, Priscilla De La; Campbell, Joannalee; Fama, Chris; Haller, Jessica; Ramirez-Zamora, Adolfo; Durphy, Jennifer; Hanspal, Era; Molho, Eric; Barba, Anne; Shin, Damian; Pilitsis, Julie G.

    2015-01-01

    Background At least 14% of Parkinson disease (PD) patients develop impulse control disorders (ICDs). The pathophysiology behind these behaviors and the impact of deep brain stimulation in a real-life setting remains unclear. Objectives We prospectively examined the impact of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) on ICDs in PD patients, as well as the relationship between impaired sensorimotor gaiting and impulsivity. Methods Patients undergoing bilateral STN-DBS were assessed for ICDs preoperatively and 1-year postoperatively using a validated questionnaire (QUIP-RS). A subset of patients completed the Balloon Analog Risk Task (BART) and auditory pre-pulse inhibition (PPI) testing. Results Analysis revealed 12 patients had an improvement in score assessing ICDs (“good responders” – GR; p = 0.006) while 4 had a worse or stable score (“poor responders” – PR; p > 0.05). GR further exemplified a significant decrease in hypersexual behavior (p = 0.005) and binge eating (p = 0.01). Impaired PPI responses also significantly correlated with impulsivity in BART (r = −0.72, p = 0.044). Discussion Following bilateral STN-DBS 75% of our cohort had a reduction in ICDs, thus suggesting deep brain stimulation effectively manages ICDs in PD. The role of impaired PPI in predisposition to ICDs in PD warrants further investigation. PMID:26066569

  16. Improvement of Advanced Parkinson’s Disease Manifestations with Deep Brain Stimulation of the Subthalamic Nucleus: A Single Institution Experience

    PubMed Central

    Rabie, Ahmed; Verhagen Metman, Leo; Fakhry, Mazen; Eassa, Ayman Youssef Ezeldin; Fouad, Wael; Shakal, Ahmed; Slavin, Konstantin V.

    2016-01-01

    We present our experience at the University of Illinois at Chicago (UIC) in deep brain stimulation (DBS) of the subthalamic nucleus (STN), describing our surgical technique, and reporting our clinical results, and morbidities. Twenty patients with advanced Parkinson’s disease (PD) who underwent bilateral STN-DBS were studied. Patients were assessed preoperatively and followed up for one year using the Unified Parkinson’s Disease Rating Scale (UPDRS) in “on” and “off” medication and “on” and “off” stimulation conditions. At one-year follow-up, we calculated significant improvement in all the motor aspects of PD (UPDRS III) and in activities of daily living (UPDRS II) in the “off” medication state. The “off” medication UPDRS improved by 49.3%, tremors improved by 81.6%, rigidity improved by 50.0%, and bradykinesia improved by 39.3%. The “off” medication UPDRS II scores improved by 73.8%. The Levodopa equivalent daily dose was reduced by 54.1%. The UPDRS IVa score (dyskinesia) was reduced by 65.1%. The UPDRS IVb score (motor fluctuation) was reduced by 48.6%. Deep brain stimulation of the STN improves the cardinal motor manifestations of the idiopathic PD. It also improves activities of daily living, and reduces medication-induced complications. PMID:27983589

  17. Successful Management of Hemorrhage-Associated Hemiballism After Subthalamic Nucleus Deep Brain Stimulation with Pallidal Stimulation: a Case Report.

    PubMed

    Pabaney, Aqueel; Ali, Rushna; Lewitt, Peter A; Sidiropoulos, Christos; Schwalb, Jason M

    2015-10-01

    Deep brain stimulation has been widely used for treating several movement disorders including idiopathic Parkinson disease (IPD). The development of hemiballism after an iatrogenic injury to the subthalamic nucleus (STN) such as postoperative hemorrhage or stroke is rare. Employing pallidal DBS to manage hemiballism arising as a result of STN injury is a unique application of this therapeutic modality, which has only been reported twice in the literature. We present a case of a 54-year-old male with levodopa-responsive IPD who underwent STN electrode placement for deep brain stimulation. The immediate postoperative course was uneventful, but the patient suffered a fall 12 weeks after electrode implantation, leading to electrode displacement and subsequent STN hemorrhage, which led to hemiballism. The hemiballism was then subsequently treated with pallidal DBS after medical management was unsuccessful. In our case pallidal DBS was effective in treating hemiballism that arose as a result of traumatic displacement of STN DBS electrodes. Medical management and changes in stimulation parameters failed to produce any significant change in the hemiballism. This report is only the third of its kind in the literature wherein hemiballism arising as a result of STN damage after DBS was successfully treated with pallidal stimulation. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Improvement of Advanced Parkinson's Disease Manifestations with Deep Brain Stimulation of the Subthalamic Nucleus: A Single Institution Experience.

    PubMed

    Rabie, Ahmed; Verhagen Metman, Leo; Fakhry, Mazen; Eassa, Ayman Youssef Ezeldin; Fouad, Wael; Shakal, Ahmed; Slavin, Konstantin V

    2016-12-13

    We present our experience at the University of Illinois at Chicago (UIC) in deep brain stimulation (DBS) of the subthalamic nucleus (STN), describing our surgical technique, and reporting our clinical results, and morbidities. Twenty patients with advanced Parkinson's disease (PD) who underwent bilateral STN-DBS were studied. Patients were assessed preoperatively and followed up for one year using the Unified Parkinson's Disease Rating Scale (UPDRS) in "on" and "off" medication and "on" and "off" stimulation conditions. At one-year follow-up, we calculated significant improvement in all the motor aspects of PD (UPDRS III) and in activities of daily living (UPDRS II) in the "off" medication state. The "off" medication UPDRS improved by 49.3%, tremors improved by 81.6%, rigidity improved by 50.0%, and bradykinesia improved by 39.3%. The "off" medication UPDRS II scores improved by 73.8%. The Levodopa equivalent daily dose was reduced by 54.1%. The UPDRS IVa score (dyskinesia) was reduced by 65.1%. The UPDRS IVb score (motor fluctuation) was reduced by 48.6%. Deep brain stimulation of the STN improves the cardinal motor manifestations of the idiopathic PD. It also improves activities of daily living, and reduces medication-induced complications.

  19. Subthalamic nucleus deep brain stimulation induces impulsive action when patients with Parkinson's disease act under speed pressure.

    PubMed

    Pote, Inês; Torkamani, Mariam; Kefalopoulou, Zinovia-Maria; Zrinzo, Ludvic; Limousin-Dowsey, Patricia; Foltynie, Thomas; Speekenbrink, Maarten; Jahanshahi, Marjan

    2016-07-01

    The subthalamic nucleus (STN) is proposed to modulate response thresholds and speed-accuracy trade-offs. In situations of conflict, the STN is considered to raise response thresholds, allowing time for the accumulation of information to occur before a response is selected. Conversely, speed pressure is thought to reduce the activity of the STN and lower response thresholds, resulting in fast, errorful responses. In Parkinson's disease (PD), subthalamic nucleus deep brain stimulation (STN-DBS) reduces the activity of the nucleus and improves motor symptoms. We predicted that the combined effects of STN stimulation and speed pressure would lower STN activity and lead to fast, errorful responses, hence resulting in impulsive action. We used the motion discrimination 'moving-dots' task to assess speed-accuracy trade-offs, under both speed and accuracy instructions. We assessed 12 patients with PD and bilateral STN-DBS and 12 age-matched healthy controls. Participants completed the task twice, and the patients completed it once with STN-DBS on and once with STN-DBS off, with order counterbalanced. We found that STN stimulation was associated with significantly faster reaction times but more errors under speed instructions. Application of the drift diffusion model showed that stimulation resulted in lower response thresholds when acting under speed pressure. These findings support the involvement of the STN in the modulation of speed-accuracy trade-offs and establish for the first time that speed pressure alone, even in the absence of conflict, can result in STN stimulation inducing impulsive action in PD.

  20. Resonant antidromic cortical circuit activation as a consequence of high-frequency subthalamic deep-brain stimulation.

    PubMed

    Li, S; Arbuthnott, G W; Jutras, M J; Goldberg, J A; Jaeger, D

    2007-12-01

    Deep brain stimulation (DBS) is an effective treatment of Parkinson's disease (PD) for many patients. The most effective stimulation consists of high-frequency biphasic stimulation pulses around 130 Hz delivered between two active sites of an implanted depth electrode to the subthalamic nucleus (STN-DBS). Multiple studies have shown that a key effect of STN-DBS that correlates well with clinical outcome is the reduction of synchronous and oscillatory activity in cortical and basal ganglia networks. We hypothesized that antidromic cortical activation may provide an underlying mechanism responsible for this effect, because stimulation is usually performed in proximity to cortical efferent pathways. We show with intracellular cortical recordings in rats that STN-DBS did in fact lead to antidromic spiking of deep layer cortical neurons. Furthermore, antidromic spikes triggered a dampened oscillation of local field potentials in cortex with a resonant frequency around 120 Hz. The amplitude of antidromic activation was significantly correlated with an observed suppression of slow wave and beta band activity during STN-DBS. These findings were seen in ketamine-xylazine or isoflurane anesthesia in both normal and 6-hydroxydopamine (6-OHDA)-lesioned rats. Thus antidromic resonant activation of cortical microcircuits may make an important contribution toward counteracting the overly synchronous and oscillatory activity characteristic of cortical activity in PD.

  1. Functional MRI reveals frequency-dependent responses during deep brain stimulation at the subthalamic nucleus or internal globus pallidus.

    PubMed

    Lai, Hsin-Yi; Younce, John R; Albaugh, Daniel L; Kao, Yu-Chieh Jill; Shih, Yen-Yu Ian

    2014-01-01

    Deep brain stimulation (DBS) represents a widely used therapeutic tool for the symptomatic treatment of movement disorders, most commonly Parkinson's disease (PD). High frequency stimulation at both the subthalamic nucleus (STN) and internal globus pallidus (GPi) has been used with great success for the symptomatic treatment of PD, although the therapeutic mechanisms of action remain elusive. To better understand how DBS at these target sites modulates neural circuitry, the present study used functional blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to map global brain responses to DBS at the STN and GPi of the rat. Robust activation centered in the ipsilateral motor cortex was observed during high frequency stimulation at either target site, with peak responses observed at a stimulation frequency of 100Hz. Of note, frequency tuning curves were generated, demonstrating that cortical activation was maximal at clinically-relevant stimulation frequencies. Divergent responses to stimulation were noted in the contralateral hemisphere, with strong cortical and striatal negative BOLD signal during stimulation of the GPi, but not STN. The frequency-dependence of the observed motor cortex activation at both targets suggests a relationship with the therapeutic effects of STN and GPi DBS, with both DBS targets being functionally connected with motor cortex at therapeutic stimulation frequencies.

  2. Effects of subthalamic deep brain stimulation on noun/verb generation and selection from competing alternatives in Parkinson's disease.

    PubMed

    Castner, J E; Chenery, H J; Silburn, P A; Coyne, T J; Sinclair, F; Smith, E R; Copland, D A

    2008-06-01

    Impaired generation of verbs relative to nouns has been reported in Parkinson's disease (PD) and has been associated with the frontal pathophysiology of PD. The aim of the present study was to measure noun/verb generation abilities in PD and to determine whether noun/verb generation is affected by stimulation of the subthalamic nucleus (STN). 8 participants who had been diagnosed with PD and had received surgery for deep brain stimulation (DBS) of the STN as well as 15 control participants completed a noun/verb generation task with four probe-response conditions-namely, noun-noun, verb-noun, noun-verb and verb-verb conditions. Patients with PD were assessed while receiving STN stimulation and without stimulation. During the off stimulation condition, patients with PD presented with a selective deficit in verb generation compared with control participants. However, when receiving STN stimulation, patients with PD produced significantly more errors than controls during the noun-noun and verb-verb conditions, supporting evidence from previous studies that STN stimulation modulates a frontotemporal network associated with word generation. Finally, errors during verb generation were significantly correlated with item selection constraint (ie, the degree to which a response competes with other response alternatives) in the on stimulation condition, but not the off stimulation condition. Our results suggest that STN stimulation affects the ability to select from many competing lexical alternatives during verb generation.

  3. Characteristic laryngoscopic findings in Parkinson's disease patients after subthalamic nucleus deep brain stimulation and its correlation with voice disorder.

    PubMed

    Tsuboi, Takashi; Watanabe, Hirohisa; Tanaka, Yasuhiro; Ohdake, Reiko; Yoneyama, Noritaka; Hara, Kazuhiro; Ito, Mizuki; Hirayama, Masaaki; Yamamoto, Masahiko; Fujimoto, Yasushi; Kajita, Yasukazu; Wakabayashi, Toshihiko; Sobue, Gen

    2015-12-01

    Speech and voice disorders are one of the most common adverse effects in Parkinson's disease (PD) patients treated with subthalamic nucleus deep brain stimulation (STN-DBS). However, the pathophysiology of voice and laryngeal dysfunction after STN-DBS remains unclear. We assessed 47 PD patients (22 treated with bilateral STN-DBS (PD-DBS) and 25 treated medically (PD-Med); all patients in both groups matched by age, sex, disease duration, and motor and cognitive function) using the objective and subjective voice assessment batteries (GRBAS scale and Voice Handicap Index), and laryngoscopy. Laryngoscopic examinations revealed that PD-DBS patients showed a significantly higher incidence of incomplete glottal closure (77 vs 48 %; p = 0.039), hyperadduction of the false vocal folds (73 vs 44 %; p = 0.047), anteroposterior hypercompression (50 vs 20 %; p = 0.030) and asymmetrical glottal movement (50 vs 16 %; p = 0.002) than PD-Med patients. On- and off-stimulation assessment revealed that STN-DBS could induce or aggravate incomplete glottal closure, hyperadduction of the false vocal folds, anteroposterior hypercompression, and asymmetrical glottal movement. Incomplete glottal closure and hyperadduction of the false vocal folds significantly correlated with breathiness and strained voice, respectively (r = 0.590 and 0.539). We should adjust patients' DBS settings in consideration of voice and laryngeal functions as well as motor function.

  4. Cognitive Changes following Bilateral Deep Brain Stimulation of Subthalamic Nucleus in Parkinson's Disease: A Meta-Analysis.

    PubMed

    Xie, Yi; Meng, Xiangyu; Xiao, Jinsong; Zhang, Jie; Zhang, Junjian

    2016-01-01

    Background. Nowadays, it has been largely acknowledged that deep brain stimulation of subthalamic nucleus (STN DBS) can alleviate motor symptoms of Parkinson's disease, but its effects on cognitive function remain unclear, which are not given enough attention by many clinical doctors and researchers. To date, 3 existing meta-analyses focusing on this issue included self-control studies and have not drawn consistent conclusions. The present study is the first to compare effect sizes of primary studies that include control groups, hoping to reveal the net cognitive outcomes after STN DBS and the clinical significance. Methods. A structured literature search was conducted using strict criteria. Only studies with control group could be included. Data on age, duration of disease, levodopa equivalent dosage (LED), and multiple cognitive scales were collected and pooled. Results. Of 172 articles identified, 10 studies (including 3 randomized controlled trials and 7 nonrandomized controlled studies) were eligible for inclusion. The results suggest that STN DBS results in decreased global cognition, memory, verbal fluency, and executive function compared with control group. No significant difference is found in other cognitive domains. Conclusions. STN DBS seems relatively safe with respect to cognitive function, and further studies should focus on the exact mechanisms of possible verbal deterioration after surgery in the future.

  5. Subthalamic deep brain stimulation reduces pathological information transmission to the thalamus in a rat model of parkinsonism.

    PubMed

    Anderson, Collin J; Sheppard, Daylan T; Huynh, Rachel; Anderson, Daria Nesterovich; Polar, Christian A; Dorval, Alan D

    2015-01-01

    The degeneration of dopaminergic neurons in the substantia nigra pars compacta leads to parkinsonian motor symptoms via changes in electrophysiological activity throughout the basal ganglia. High-frequency deep brain stimulation (DBS) partially treats these symptoms, but the mechanisms are unclear. We hypothesize that motor symptoms of Parkinson's disease (PD) are associated with increased information transmission from basal ganglia output neurons to motor thalamus input neurons and that therapeutic DBS of the subthalamic nucleus (STN) treats these symptoms by reducing this extraneous information transmission. We tested these hypotheses in a unilateral, 6-hydroxydopamine-lesioned rodent model of hemiparkinsonism. Information transfer between basal ganglia output neurons and motor thalamus input neurons increased in both the orthodromic and antidromic directions with hemiparkinsonian (hPD) onset, and these changes were reversed by behaviorally therapeutic STN-DBS. Omnidirectional information increases in the parkinsonian state underscore the detrimental nature of that pathological information and suggest a loss of information channel independence. Therapeutic STN-DBS reduced that pathological information, suggesting an effective increase in the number of independent information channels. We interpret these data with a model in which pathological information and fewer information channels diminishes the scope of possible motor activities, driving parkinsonian symptoms. In this model, STN-DBS restores information-channel independence by eliminating or masking the parkinsonism-associated information, and thus enlarges the scope of possible motor activities, alleviating parkinsonian symptoms.

  6. Characterizing effects of subthalamic nucleus deep brain stimulation on methamphetamine-induced circling behavior in hemi-Parkinsonian rats.

    PubMed

    So, Rosa Q; McConnell, George C; August, Auriel T; Grill, Warren M

    2012-09-01

    The unilateral 6-hydroxydopamine (6-OHDA) lesioned rat model is frequently used to study the effects of subthalamic nucleus (STN) deep brain stimulation (DBS) for the treatment of Parkinson's disease. However, systematic knowledge of the effects of DBS parameters on behavior in this animal model is lacking. The goal of this study was to characterize the effects of DBS on methamphetamine-induced circling in the unilateral 6-OHDA lesioned rat. DBS parameters tested include stimulation amplitude, stimulation frequency, methamphetamine dose, stimulation polarity, and anatomical location of the electrode. When an appropriate stimulation amplitude and dose of methamphetamine were applied, high-frequency stimulation (> 130 Hz), but not low frequency stimulation (< 10 Hz), reversed the bias in ipsilateral circling without inhibiting movement. This characteristic frequency tuning profile was only generated when at least one electrode used during bipolar stimulation was located within the STN. No difference was found between bipolar stimulation and monopolar stimulation when the most effective electrode contact was selected, indicating that monopolar stimulation could be used in future experiments. Methamphetamine-induced circling is a simple, reliable, and sensitive behavioral test and holds potential for high-throughput study of the effects of STN DBS in unilaterally lesioned rats.

  7. Programming for Stimulation-Induced Transient Nonmotor Psychiatric Symptoms after Bilateral Subthalamic Nucleus Deep Brain Stimulation for Parkinson's Disease

    PubMed Central

    Wu, Xi; Qiu, Yiqing; Simfukwe, Keith; Wang, Jiali; Chen, Jianchun

    2017-01-01

    Background Stimulation-induced transient nonmotor psychiatric symptoms (STPSs) are side effects following bilateral subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD) patients. We designed algorithms which (1) determine the electrode contacts that induce STPSs and (2) provide a programming protocol to eliminate STPS and maintain the optimal motor functions. Our objective is to test the effectiveness of these algorithms. Materials and Methods 454 PD patients who underwent programming sessions after STN-DBS implantations were retrospectively analyzed. Only STPS patients were enrolled. In these patients, the contacts inducing STPS were found and the programming protocol algorithms used. Results Eleven patients were diagnosed with STPS. Of these patients, two had four episodes of crying, and two had four episodes of mirthful laughter. In one patient, two episodes of abnormal sense of spatial orientation were observed. Hallucination episodes were observed twice in one patient, while five patients recorded eight episodes of hypomania. There were no statistical differences between the UPDRS-III under the final stimulation parameter (without STPS) and previous optimum UPDRS-III under the STPSs (p = 1.000). Conclusion The flow diagram used for determining electrode contacts that induce STPS and the programming protocol employed in the treatment of these symptoms are effective. PMID:28894620

  8. Dorsolateral subthalamic neuronal activity enhanced by median nerve stimulation characterizes Parkinson's disease during deep brain stimulation with general anesthesia.

    PubMed

    Tsai, Sheng-Tzung; Chuang, Wei-Yi; Kuo, Chung-Chih; Chao, Paul C P; Chen, Tsung-Ying; Hung, Hsiang-Yi; Chen, Shin-Yuan

    2015-12-01

    Deep brain stimulation (DBS) surgery under general anesthesia is an alternative option for patients with Parkinson's disease (PD). However, few studies are available that report whether neuronal firing can be accurately recorded during this condition. In this study the authors attempted to characterize the neuronal activity of the subthalamic nucleus (STN) and elucidate the influence of general anesthetics on neurons during DBS surgery in patients with PD. The benefit of median nerve stimulation (MNS) for localization of the dorsolateral subterritory of the STN, which is involved in sensorimotor function, was explored. Eight patients with PD were anesthetized with desflurane and underwent contralateral MNS at the wrist during microelectrode recording of the STN. The authors analyzed the spiking patterns and power spectral density (PSD) of the background activity along each penetration track and determined the spatial correlation to the target location, estimated mated using standard neurophysiological procedures. The dorsolateral STN spiking pattern showed a more prominent bursting pattern without MNS and more oscillation with MNS. In terms of the neural oscillation of the background activity, beta-band oscillation dominated within the sensorimotor STN and showed significantly more PSD during MNS (p < 0.05). Neuronal firing within the STN could be accurately identified and differentiated when patients with PD received general anesthetics. Median nerve stimulation can enhance the neural activity in beta-band oscillations, which can be used as an index to ensure optimal electrode placement via successfully tracked dorsolateral STN topography.

  9. Intensive Voice Treatment (LSVT®LOUD) for Parkinson’s disease following Deep Brain Stimulation of the Subthalamic Nucleus

    PubMed Central

    Spielman, Jennifer; Mahler, Leslie; Halpern, Angela; Gilley, Phllip; Klepitskaya, Olga; Ramig, Lorraine

    2011-01-01

    Purpose Intensive voice therapy (LSVT®LOUD) can effectively manage voice and speech symptoms associated with idiopathic Parkinson disease (PD). This small-group study evaluated voice and speech in individuals with and without deep brain stimulation of the subthalamic nucleus (STN-DBS) before and after LSVT LOUD, to determine whether outcomes for surgical subjects were comparable to non-surgical cohorts. Methods Eight subjects with PD (four with STN-DBS and four without) received LSVT LOUD four times a week for four weeks. Four additional subjects with PD remained untreated. Voice intensity (SPL), Vowel Articulation Index (VAI), the Voice Handicap Index (VHI), and a structured interview were evaluated before and after treatment and again six months later. Results Both treated groups showed significant increases in SPL from pre to post and six-month follow up. VAI was significantly higher for the treated groups compared to the untreated subjects at follow up. Several treated individuals had significant clinical improvement in VHI scores, particularly within the LSVT-DBS group. Treated individuals reported improvements in voice and speech in structured interviews; however, answers suggest more variable long-term maintenance within the LSVT-DBS group. The untreated group exhibited no significant changes in any measure throughout the study. Conclusions Results support LSVT LOUD for treating voice and speech in individuals with PD following STN-DBS surgery. However, modifications may be required to maintain functional improvements. PMID:21724193

  10. Comparison of Globus Pallidus Interna and Subthalamic Nucleus in Deep Brain Stimulation for Parkinson Disease: An Institutional Experience and Review

    PubMed Central

    Yazdani, Umar; Dewey III, Richard; Dewey, Richard B.; Miocinovic, Svjetlana

    2017-01-01

    Deep Brain Stimulation (DBS) has revolutionized the lives of patients of Parkinson disease, offering therapeutic options to those not benefiting entirely from medications alone. With its proven track record of outperforming the best medical management, the goal is to unlock the full potential of this therapy. Currently, the Globus Pallidus Interna (GPi) and Subthalamic Nucleus (STN) are both viable targets for DBS, and the choice of site should focus on the constellation of symptoms, both motor and nonmotor, which are key determinants to quality of life. Our article sheds light on the specific advantages and drawbacks of the two sites, highlighting the need for matching the inherent properties of a target with specific desired effects in patients. UT Southwestern Medical Center has a robust and constantly evolving DBS program and the narrative from our center provides invaluable insight into the practical realities of DBS. The ultimate decision in selecting a DBS target is complex, ideally made by a multidisciplinary team, tailored towards each patient's profile and their expectations, by drawing upon scientific evidence coupled with experience. Ongoing research is expanding our knowledge base, which should be dynamically incorporated into an institute's DBS paradigm to ensure that patients receive the optimal therapy. PMID:28706748

  11. Subthalamic Nucleus Deep Brain Stimulation in Early Stage Parkinson's Disease Is Not Associated with Increased Body Mass Index.

    PubMed

    Millan, Sarah H; Hacker, Mallory L; Turchan, Maxim; Molinari, Anna L; Currie, Amanda D; Charles, David

    2017-01-01

    Previous studies suggest that deep brain stimulation of the subthalamic nucleus (STN-DBS) for Parkinson's disease (PD) leads to weight gain. This study analyzes changes in body mass index (BMI) in 29 subjects from a prospective, single-blind trial of DBS in early stage PD (age 50-75, Hoehn & Yahr stage II off medication, treated with antiparkinsonian medications for ≥6 months but <4 years, and without a history of motor fluctuations, dyskinesias, or dementia). Subjects were randomized to DBS plus optimal drug therapy (DBS+ODT; n = 15) or ODT (n = 14) and followed for 24 months. Weight and height were recorded at baseline and each follow-up visit and used to calculate BMI. BMIs were compared within and between groups using nonparametric t-tests. Mean BMI at baseline was 29.7 in the ODT group and 32.3 in the DBS+ODT group (p > 0.05). BMI change over two years was not different between the groups (p = 0.62, ODT = -0.89; DBS+ODT = -0.17). This study suggests that STN-DBS is not associated with weight gain in subjects with early stage PD. This finding will be tested in an upcoming FDA-approved phase III multicenter, randomized, double-blind, placebo-controlled, pivotal clinical trial evaluating DBS in early stage PD (ClinicalTrials.gov identifier NCT00282152).

  12. Modulations on cortical oscillations by subthalamic deep brain stimulation in patients with Parkinson disease: A MEG study.

    PubMed

    Cao, Chun-Yan; Zeng, Ke; Li, Dian-You; Zhan, Shi-Kun; Li, Xiao-Li; Sun, Bo-Min

    2017-01-01

    The study aimed to explore the modification to cortical oscillations of Parkinson disease (PD) patients by subthalamic nucleus deep brain stimulation (STN DBS). With Magnetoencephalogram (MEG) detection, we examined the changes in absolute power spectrum of cortical oscillations in the PD patients with the treatment of STN DBS. The power analysis of PD patients showed a dominant over-synchronization of alpha and beta bands in temporal and occipital areas relative to the healthy control subjects. STN DBS on-state showed marked power increase in the gamma band of PD patients in the frontal and parietal relative to the DBS off-state. The alleviation of motor symptoms by STN DBS negatively correlated to the increase of high gamma oscillation in the right frontal cortex, and also correlated to the suppression of the alpha and beta oscillations in the right temporal cortex. The treatment of STN DBS to PD patients might involve the augmentation of gamma activity and suppression of alpha and beta activities in cortical oscillations. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. Subthalamic deep brain stimulation restores automatic response activation and increases susceptibility to impulsive behavior in patients with Parkinson's disease.

    PubMed

    Plessow, Franziska; Fischer, Rico; Volkmann, Jens; Schubert, Torsten

    2014-06-01

    Repeatedly reported deficits of patients with Parkinson's disease (PD) in selecting an appropriate action in the face of competing response alternatives has led to the conclusion of a basal ganglia (BG) involvement in response selection and impulse control. Despite capacious research, it remains elusive how BG dysfunction affects processes subserving goal-directed behavior. Even more problematically, since PD pathology transcends a BG dysfunction due to dopamine depletion in the nigrostriatal DA system (by also comprising alterations in extrastriatal dopamine availability and other neurotransmitter systems), it is not yet clear which aspects of these deficits are actually caused by BG dysfunction. To address this question, the present study investigated 13 off-medication PD patients with bilateral therapeutic subthalamic deep brain stimulation (DBS) both with and without stimulation (DBSON and DBSOFF, respectively) and 26 healthy controls. All participants performed a task that tests the relation between automatic response impulses and goal-directed action selection. Results show an improvement of automatic response activation under DBSON, increasing the susceptibility to impulsive responses, and a reduced impact of automatic response activation under DBSOFF. We argue that the BG determine the efficiency of the regulation and transmission of stimulus-driven bottom-up response activation required for efficient response selection.

  14. Deep Brain Stimulation of Caudal Zona Incerta and Subthalamic Nucleus in Patients with Parkinson's Disease: Effects on Diadochokinetic Rate

    PubMed Central

    Karlsson, Fredrik; Unger, Elin; Wahlgren, Sofia; Blomstedt, Patric; Linder, Jan; Nordh, Erik; Zafar, Hamayun; van Doorn, Jan

    2011-01-01

    The hypokinetic dysarthria observed in Parkinson's disease (PD) affects the range, speed, and accuracy of articulatory gestures in patients, reducing the perceived quality of speech acoustic output in continuous speech. Deep brain stimulation (DBS) of the subthalamic nucleus (STN-DBS) and of the caudal zona incerta (cZi-DBS) are current surgical treatment options for PD. This study aimed at investigating the outcome of STN-DBS (7 patients) and cZi-DBS (7 patients) in two articulatory diadochokinesis tasks (AMR and SMR) using measurements of articulation rate and quality of the plosive consonants (using the percent measurable VOT metric). The results indicate that patients receiving STN-DBS increased in articulation rate in the Stim-ON condition in the AMR task only, with no effect on production quality. Patients receiving cZi-DBS decreased in articulation rate in the Stim-ON condition and further showed a reduction in production quality. The data therefore suggest that cZi-DBS is more detrimental for extended articulatory movements than STN-DBS. PMID:22007342

  15. The effects of unilateral versus bilateral subthalamic nucleus deep brain stimulation on prosaccades and antisaccades in Parkinson's disease.

    PubMed

    Goelz, Lisa C; David, Fabian J; Sweeney, John A; Vaillancourt, David E; Poizner, Howard; Metman, Leonard Verhagen; Corcos, Daniel M

    2017-02-01

    Unilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with Parkinson's disease improves skeletomotor function assessed clinically, and bilateral STN DBS improves motor function to a significantly greater extent. It is unknown whether unilateral STN DBS improves oculomotor function and whether bilateral STN DBS improves it to a greater extent. Further, it has also been shown that bilateral, but not unilateral, STN DBS is associated with some impaired cognitive-motor functions. The current study compared the effect of unilateral and bilateral STN DBS on sensorimotor and cognitive aspects of oculomotor control. Patients performed prosaccade and antisaccade tasks during no stimulation, unilateral stimulation, and bilateral stimulation. There were three sets of findings. First, for the prosaccade task, unilateral STN DBS had no effect on prosaccade latency and it reduced prosaccade gain; bilateral STN DBS reduced prosaccade latency and increased prosaccade gain. Second, for the antisaccade task, neither unilateral nor bilateral stimulation had an effect on antisaccade latency, unilateral STN DBS increased antisaccade gain, and bilateral STN DBS increased antisaccade gain to a greater extent. Third, bilateral STN DBS induced an increase in prosaccade errors in the antisaccade task. These findings suggest that while bilateral STN DBS benefits spatiotemporal aspects of oculomotor control, it may not be as beneficial for more complex cognitive aspects of oculomotor control. Our findings are discussed considering the strategic role the STN plays in modulating information in the basal ganglia oculomotor circuit.

  16. Choreatic Side Effects of Deep Brain Stimulation of the Anteromedial Subthalamic Nucleus for Treatment-Resistant Obsessive-Compulsive disorder.

    PubMed

    Mulders, Anne E P; Leentjens, Albert F G; Schruers, Koen; Duits, Annelien; Ackermans, Linda; Temel, Yasin

    2017-08-01

    Patients with treatment-resistant obsessive-compulsive disorder (OCD) are potential candidates for deep brain stimulation (DBS). The anteromedial subthalamic nucleus (STN) is among the most commonly used targets for DBS in OCD. We present a patient with a 30-year history of treatment-resistant OCD who underwent anteromedial STN-DBS. Despite a clear mood-enhancing effect, stimulation caused motor side effects, including bilateral hyperkinesia, dyskinesias, and sudden large amplitude choreatic movements of arms and legs when stimulating at voltages greater than approximately 1.5 V. DBS at lower amplitudes and at other contact points failed to result in a significant reduction of obsessions and compulsions without inducing motor side effects. Because of this limitation in programming options, we decided to reoperate and target the ventral capsule/ventral striatum (VC/VS), which resulted in a substantial reduction in key obsessive and compulsive symptoms without serious side effects. Choreatic movements and hemiballismus have previously been linked to STN dysfunction and have been incidentally reported as side effects of DBS of the dorsolateral STN in Parkinson disease (PD). However, in PD, these side effects were usually transient, and they rarely interfered with DBS programming. In our patient, the motor side effects were persistent, and they made optimal DBS programming impossible. To our knowledge, such severe and persistent motor side effects have not been described previously for anteromedial STN-DBS. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. A functionally relevant and long-term model of deep brain stimulation of the rat subthalamic nucleus: advantages and considerations.

    PubMed

    Spieles-Engemann, A L; Collier, T J; Sortwell, C E

    2010-10-01

    In this review we outline some relevant considerations with regards to the rat model of deep brain stimulation of the subthalamic nucleus (STN DBS). In order to optimize the rat STN DBS model in terms of predictive validity for the clinical situation we propose that the STN stimulation experimental design parameters in rodents should incorporate the following features: (i) stimulation parameters that demonstrate functional alleviation of symptoms induced by nigrostriatal dopamine (DA) denervation; (ii) stimulation duration that is relatively long-term and continuous; (iii) stimulation that is initiated at a time when the denervation status of the nigrostriatal system is known to be partial and progressing; (iv) stimulation current spread that is minimized and optimized to closely approximate the clinical situation; (v) the appropriate control conditions are included; and (vi) implantation to the STN target is verified post-mortem. Further research that examines the effect of long-term STN DBS on the neurophysiology and neurochemistry of STN circuitry is warranted. The rat model of functionally relevant long-term STN DBS provides a most favorable preclinical experimental platform in which to conduct these studies.

  18. Subthalamic deep brain stimulation reduces pathological information transmission to the thalamus in a rat model of parkinsonism

    PubMed Central

    Anderson, Collin J.; Sheppard, Daylan T.; Huynh, Rachel; Anderson, Daria Nesterovich; Polar, Christian A.; Dorval, Alan D.

    2015-01-01

    The degeneration of dopaminergic neurons in the substantia nigra pars compacta leads to parkinsonian motor symptoms via changes in electrophysiological activity throughout the basal ganglia. High-frequency deep brain stimulation (DBS) partially treats these symptoms, but the mechanisms are unclear. We hypothesize that motor symptoms of Parkinson’s disease (PD) are associated with increased information transmission from basal ganglia output neurons to motor thalamus input neurons and that therapeutic DBS of the subthalamic nucleus (STN) treats these symptoms by reducing this extraneous information transmission. We tested these hypotheses in a unilateral, 6-hydroxydopamine-lesioned rodent model of hemiparkinsonism. Information transfer between basal ganglia output neurons and motor thalamus input neurons increased in both the orthodromic and antidromic directions with hemiparkinsonian (hPD) onset, and these changes were reversed by behaviorally therapeutic STN-DBS. Omnidirectional information increases in the parkinsonian state underscore the detrimental nature of that pathological information and suggest a loss of information channel independence. Therapeutic STN-DBS reduced that pathological information, suggesting an effective increase in the number of independent information channels. We interpret these data with a model in which pathological information and fewer information channels diminishes the scope of possible motor activities, driving parkinsonian symptoms. In this model, STN-DBS restores information-channel independence by eliminating or masking the parkinsonism-associated information, and thus enlarges the scope of possible motor activities, alleviating parkinsonian symptoms. PMID:26217192

  19. What is the best treatment for fluctuating Parkinson's disease: continuous drug delivery or deep brain stimulation of the subthalamic nucleus?

    PubMed

    Hilker, Rüdiger; Antonini, Angelo; Odin, Per

    2011-06-01

    Motor complications impair quality of life and cause severe disability in patients with advanced Parkinson's disease (PD). Since they are often refractory to medical therapy, interventional therapies have been developed, which can provide a considerable reduction of daily off-time and dopaminergic dyskinesias. Continuous dopaminergic drug delivery (CDD) is based on the steady stimulation of striatal dopamine receptors by subcutaneous apomorphine or duodenal L: -DOPA infusions via portable minipumps. Advances in the understanding of basal ganglia functioning and in neurosurgical, electrophysiological and neuroimaging techniques have led to a renaissance of neurosurgery for advanced PD. Deep brain stimulation of the subthalamic nucleus (STN-DBS) is the most invasive procedure promising great benefit and the highest level of independency for suitable patients, but is definitely associated with surgical risks and DBS-related side effects. Each of these more or less invasive therapy options has its own profile, and a thorough consideration of its advantages and drawbacks for the individual situation is mandatory. In this paper, we summarize relevant facts for this decision and provide some guidelines for a responsible counseling of eligible patients.

  20. Effects of contact location and voltage amplitude on speech and movement in bilateral subthalamic nucleus deep brain stimulation.

    PubMed

    Tripoliti, Elina; Zrinzo, Ludvic; Martinez-Torres, Irene; Tisch, Stephen; Frost, Eleanor; Borrell, Ellie; Hariz, Marwan I; Limousin, Patricia

    2008-12-15

    Subthalamic nucleus deep brain stimulation (STN-DBS) is particularly effective in improving limb symptoms in Parkinson's disease. However, speech shows a variable response. Contact site and amplitude of stimulation have been suggested as possible factors influencing speech. In this double blind study, we assessed 14 patients post bilateral STN-DBS, without medication. Six conditions were studied in random order as follows: stimulation inside the STN at low voltage (2 V) and at high voltage (4 V); above the STN at 2 V and at 4 V, at usual clinical parameters, and off-stimulation. The site of stimulation was defined on the postoperative stereotactic MRI data. Speech protocol consisted of the assessment of intelligibility of the dysarthric speech, maximum sustained phonation, and a 1-minute monologue. Movement was assessed using the UPDRS-III. Stimulation at 4 V significantly reduced the speech intelligibility (P = 0.004) independently from the site of stimulation. Stimulation at 4 V significantly improved the motor function. Stimulation inside the nucleus was significantly more effective than outside the nucleus (P = 0.0006). The significant improvement in movement coupled with significant deterioration in speech intelligibility when patients are stimulated inside the nucleus at high voltage indicates a critical role for electrical stimulation parameters in speech motor control. (c) 2008 Movement Disorder Society.

  1. Characterizing Effects of Subthalamic Nucleus Deep Brain Stimulation on Methamphetamine-Induced Circling Behavior in Hemiparkinsonian Rats

    PubMed Central

    So, Rosa Q.; McConnell, George C.; August, Auriel T.; Grill, Warren M.

    2013-01-01

    The unilateral 6-hydroxydopamine (6-OHDA) lesioned rat model is frequently used to study the effects of subthalamic nucleus (STN) deep brain stimulation (DBS) for the treatment of Parkinson’s disease. However, systematic knowledge of the effects of DBS parameters on behavior in this animal model is lacking. The goal of this study was to characterize the effects of DBS on methamphetamine-induced circling in the unilateral 6-OHDA lesioned rat. DBS parameters tested include stimulation amplitude, stimulation frequency, methamphetamine dose, stimulation polarity, and anatomical location of the electrode. When an appropriate stimulation amplitude and dose of methamphetamine were applied, high frequency stimulation (> 130 Hz), but not low frequency stimulation (< 10 Hz), reversed the bias in ipsilateral circling without inhibiting movement. This characteristic frequency tuning profile was only generated when at least one electrode used during bipolar stimulation was located within the STN. No difference was found between bipolar stimulation and monopolar stimulation when the most effective electrode contact was selected, indicating that monopolar stimulation could be used in future experiments. Methamphetamine-induced circling is a simple, reliable, and sensitive behavioral test and holds potential for high-throughput study of the effects of STN DBS in unilaterally lesioned rats. PMID:22692937

  2. Deep Brain Stimulation of the subthalamic nucleus does not negatively affect social cognitive abilities of patients with Parkinson's disease.

    PubMed

    Enrici, Ivan; Mitkova, Antonia; Castelli, Lorys; Lanotte, Michele; Lopiano, Leonardo; Adenzato, Mauro

    2017-08-25

    Bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a treatment option for patients with advanced idiopathic PD successful at alleviating disabling motor symptoms. Nevertheless, the effects of STN-DBS on cognitive functions remain controversial and few studies have investigated modification of social cognitive abilities in patients with PD treated with STN-DBS. Here we expanded the typically-investigated spectrum of these abilities by simultaneously examining emotion recognition, and both affective and cognitive Theory of Mind (ToM). By means of a cross-sectional study, 20 patients with PD under dopaminergic replacement therapy, 18 patients with PD treated with STN-DBS, and 20 healthy controls performed the Ekman 60-Faces test, the full version of the Reading the Mind in the Eyes test, and the Protocol for the Attribution of Communicative Intentions. There were no differences between the PD groups (treated and not treated with STN-DBS) on any of the social cognitive tests. Our results suggest that patients with PD who are treated with STN-DBS do not experience detrimental effects on their social cognitive abilities. The present study, the first one examining a wide spectrum of social cognitive abilities after DBS of the STN, suggests that this surgical procedure can be considered safe from this standpoint.

  3. Interleaved programming of subthalamic deep brain stimulation to avoid adverse effects and preserve motor benefit in Parkinson's disease.

    PubMed

    Ramirez-Zamora, Adolfo; Kahn, Max; Campbell, Joannalee; DeLaCruz, Priscilla; Pilitsis, Julie G

    2015-03-01

    Subthalamic nucleus (STN) deep brain stimulation (DBS) is the most common surgical treatment for managing motor complications in Parkinson's disease (PD). Ultimately, outcomes depend on a variety of factors including lead location, access and expertize in programming and PD medical management. Nevertheless, achieving ideal programming settings can be difficult in certain patients, leading to suboptimal control of symptoms and stimulation-induced side effects, notably dysarthria and dyskinesia. Interleaved stimulation (ILS) is a newer programming technique that attempts to optimize the stimulation field, improving control of symptoms while minimizing stimulation-induced adverse effects. A retrospective chart review was performed on PD patients receiving STN DBS over the past 12 months. Clinical and demographic data were collected from patients identified as having received ILS. The rationale and clinical efficacy of ILS was analyzed. Nine patients received ILS due to incomplete PD symptom control or stimulation-induced side effects after attempting multiple programming options. Appropriate lead location was confirmed with postoperative MRI except in one case. Following ILS, patients reported improvement in symptoms and resolution of side effects, while preserving adequate control in Parkinsonism with a mean improvement in UPDRS-MOTOR scores of 51.2 %. ILS continues to emerge as a safe and effective programming strategy for maximizing symptom control in PD while diminishing stimulation-induced side effects.

  4. Can We Rely on Susceptibility-Weighted Imaging for Subthalamic Nucleus Identification in Deep Brain Stimulation Surgery?

    PubMed

    Bot, Maarten; Bour, Lo; de Bie, Rob M; Contarino, Maria Fiorella; Schuurman, P Richard; van den Munckhof, Pepijn

    2016-03-01

    Susceptibility-weighted imaging (SWI) offers significantly improved visibility of the subthalamic nucleus (STN) compared with traditional T2-weighted imaging. However, it is unknown whether the representation of the nucleus on SWI corresponds to the neurophysiological location of the STN. To determine the correlation between the intraoperative electrophysiological activity of the STN and the representation of the nucleus on different magnetic resonance imaging (MRI) sequences used for deep brain stimulation target planning. At stereotactic target depth, microelectrode recordings (MERs) of typical STN neuronal activity were mapped on 3 different preoperative MRI sequences: 1.5-T SWI, 1.5-T T2-weighted, and 3-T T2-weighted MRI. For each MRI sequence, it was determined whether the MER signal was situated inside or outside the contour of the STN. A total of 196 MER tracks in 34 patients were evaluated. In 165 tracks (84%), typical electrophysiological STN activity was measured. MER activity was situated more consistently inside hypointense STN contour representation on 1.5- and 3-T T2-weighted images compared with SWI (99% and 100% vs 79%, respectively). The 21% incongruence of electrophysiological STN activity outside the STN contour on SWI was seen almost exclusively in the anterior and lateral microelectrode channels. STN representation on SWI does not correspond to electrophysiological STN borders. SWI does not correctly display the lateral part of the STN. When aiming to target the superolateral sensorimotor part of the STN during deep brain stimulation surgery, SWI does not offer an advantage but a disadvantage compared with conventional T2. Future research is needed to determine whether these findings may also apply for high-field SWI.

  5. The MDS-UPDRS tracks motor and non-motor improvement due to subthalamic nucleus deep brain stimulation in Parkinson disease.

    PubMed

    Chou, Kelvin L; Taylor, Jennifer L; Patil, Parag G

    2013-11-01

    The Movement Disorders Society revision of the Unified Parkinson Disease Rating Scale (MDS-UPDRS) improves upon the original UPDRS by adding more non-motor items, making it a more robust tool to evaluate the severity of motor and non-motor symptoms of Parkinson disease. Previous studies on deep brain stimulation have not used the MDS-UPDRS. To determine if the MDS-UPDRS could detect improvement in both motor and non-motor symptoms after bilateral subthalamic nucleus deep brain stimulation for Parkinson disease. We compared scores on the entire MDS-UPDRS prior to surgery (baseline) and approximately six months following the initial programming visit in twenty subjects (12M/8F) with Parkinson disease undergoing bilateral subthalamic nucleus deep brain stimulation. STN DBS significantly improved the scores for every section of the MDS-UPDRS at the 6 month follow-up. Part I improved by 3.1 points (22%), Part II by 5.3 points (29%), Part III by 13.1 points (29%) with stimulation alone, and Part IV by 7.1 points (74%). Individual non-motor items in Part I that improved significantly were constipation, light-headedness, and fatigue. Both motor and non-motor symptoms, as assessed by the MDS-UPDRS, improve with bilateral subthalamic nucleus stimulation six months after the stimulator is turned on. We recommend that the MDS-UPDRS be utilized in future deep brain stimulation studies because of the advantage of detecting change in non-motor symptoms. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Physical activity in advanced Parkinson's disease: impact of subthalamic deep brain stimulation.

    PubMed

    Daneault, Jean-François; Sadikot, Abbas F; Barbat-Artigas, Sébastien; Aubertin-Leheudre, Mylène; Jodoin, Nicolas; Panisset, Michel; Duval, Christian

    2015-01-01

    Maintaining a physically active lifestyle promotes general health. Recent studies have demonstrated that patients with Parkinson's disease (PD) fail to meet the suggested levels of physical activity and that targeted interventions do not always improve this behavior. One validated treatment for motor symptoms in PD is subthalamic stimulation (STN DBS). Assess whether motor symptom improvement following STN DBS translated into increased physical activity behavior. Twenty patients with PD scheduled for bilateral STN DBS filled-out the Phone-FITT physical activity questionnaire and the SF-36 quality of life questionnaire prior to surgery and 6 to 9 months postoperatively. Data were compared to age- and gender-matched healthy controls. Our results demonstrate that PD patients' quality of life is significantly lower than healthy controls. While STN DBS improves motor symptoms in the intermediate term, it only improves some aspects of quality of life related to physical function. Furthermore, STN DBS does not modify physical activity behavior measured by the Phone-FITT, whether for household or recreational activities. The current study demonstrates that the motor improvements observed after STN DBS do not lead to systematic improvements in all aspects of quality of life or increased levels of physical activity. This highlights the need to develop and implement intervention strategies to promote an active lifestyle in this population, even if clinical improvement is evident following surgery.

  7. Emotion recognition in Parkinson's disease after subthalamic deep brain stimulation: differential effects of microlesion and STN stimulation.

    PubMed

    Aiello, Marilena; Eleopra, Roberto; Lettieri, Christian; Mondani, Massimo; D'Auria, Stanislao; Belgrado, Enrico; Piani, Antonella; De Simone, Luca; Rinaldo, Sara; Rumiati, Raffaella I

    2014-02-01

    Deep brain stimulation of the subthalamic nucleus (STN-DBS) has acquired a relevant role in the treatment of Parkinson's disease (PD). Despite being a safe procedure, it may expose patients to an increased risk to experience cognitive and emotional difficulties. Impairments in emotion recognition, mediated both by facial and prosodic expressions, have been reported in PD patients treated with such procedure. However, it is still unclear whether the STN per se is responsible for such changes or whether others factors like the microlesion produced by the electrode implantation may also play a role. In this study we evaluated facial emotions discrimination and emotions recognition using both facial and prosodic expressions in 12 patients with PD and 13 matched controls. Patients' were tested in four conditions: before surgery, both in on and off medication, and after surgery, respectively few days after STN implantation before turning stimulator on and few months after with stimulation on. We observed that PD patients were impaired in discriminating and recognizing facial emotions, especially disgust, even before DBS implant. Microlesion caused by surgical procedure was found to influence patients' performance on the discrimination task and recognition of sad facial expression while, after a few months of STN stimulation, impaired disgust recognition was again prominent. No impairment in emotional prosody recognition was observed both before and after surgery. Our study confirms that PD patients may experience a deficit in disgust recognition and provides insight into the differential effect of microlesion and stimulation of STN on several tasks assessing emotion recognition. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Different effectiveness of subthalamic deep brain stimulation in Parkinson's disease: A comparative cohort study at 1 year and 5 years.

    PubMed

    Jiang, Jiin-Ling; Chen, Shin-Yuan; Hsieh, Tsung-Cheng; Lee, Chi-Wei; Lin, Sheng-Huang; Tsai, Sheng-Tzung

    2015-09-01

    Subthalamic nucleus deep brain stimulation (STN-DBS) has been shown to produce long-term symptom improvement in Parkinson's disease. The aim of this study was to identify the target symptoms that show the most improvement at 1 year and at 5 years after STN-DBS. This was a 5-year cohort study of 41 consecutive patients treated with bilateral STN-DBS. Clinical evaluations were performed 1 month prior to surgery and 1 year and 5 years after surgery. The outcome measurements at 1 year and 5 years were the changes compared with the baseline in Unified Parkinson's Disease Rating Scale (UPDRS) parts I, II, III, and IV scores, the Hoehn and Yahr stage, and Schwab and England Activities of Daily Living (SEADL) scores in the conditions of off-medication/on-stimulation and off-medication/off-stimulation. Further analysis included changes in the levodopa equivalent daily dose. When compared to the preoperative baseline off-medication condition, significant improvements were observed in the UPDRS parts I, II, III, and IV and SEADL (p < 0.001) scores in the off-medication/on-stimulation condition 1 year after STN-DBS. Five years after STN-DBS, improvements in UPDRS scores were observed only for parts II, III, and IV (p < 0.001). In the off-medication/off-stimulation condition, no significant improvement was observed. At 5 years, significant deteriorations were observed in scores for the UPDRS part III axial subitem (p = 0.005), UPDRS part I (p = 0.005), UPDRS part II (p < 0.001), and SEADL (p = 0.001). The long-term effect of STN-DBS on motor function is promising, although the magnitude of its effectiveness varied over the 5-year period. Copyright © 2013. Published by Elsevier B.V.

  9. Deep-Brain Stimulation of the Subthalamic Nucleus Selectively Decreases Risky Choice in Risk-Preferring Rats.

    PubMed

    Adams, Wendy K; Vonder Haar, Cole; Tremblay, Melanie; Cocker, Paul J; Silveira, Mason M; Kaur, Sukhbir; Baunez, Christelle; Winstanley, Catharine A

    2017-01-01

    Deep brain stimulation of the subthalamic nucleus (STN-DBS) can improve the motor symptoms of Parkinson's disease (PD) and negate the problematic side effects of dopamine replacement therapy. Although there is concern that STN-DBS may enhance the development of gambling disorder and other impulse control disorders in this patient group, recent data suggest that STN-DBS may actually reduce iatrogenic impulse control disorders, and alleviate obsessive-compulsive disorder (OCD). Here, we sought to determine whether STN-DBS was beneficial or detrimental to performance of the rat gambling task (rGT), a rodent analogue of the Iowa Gambling Task (IGT) used to assess risky decision making clinically. Rats chose between four options associated with different amounts and probabilities of sugar pellet rewards versus timeout punishments. As in the IGT, the optimal approach was to favor options associated with smaller per-trial gains but lower timeout penalties. Once a stable behavioral baseline was established, electrodes were implanted bilaterally into the STN, and the effects of STN-DBS assessed on-task over 10 consecutive sessions using an A-B-A design. STN-DBS did not affect choice in optimal decision makers that correctly favored options associated with smaller per-trial gains but also lower penalties. However, a minority (∼25%) preferred the maladaptive "high-risk, high-reward" options at baseline. STN-DBS significantly and progressively improved choice in these risk-preferring rats. These data support the hypothesis that STN-DBS may be beneficial in ameliorating maladaptive decision making associated with compulsive and addiction disorders.

  10. A new biomarker for subthalamic deep brain stimulation for patients with advanced Parkinson’s disease—a pilot study

    NASA Astrophysics Data System (ADS)

    Gmel, Gerrit E.; Hamilton, Tara J.; Obradovic, Milan; Gorman, Robert B.; Single, Peter S.; Chenery, Helen J.; Coyne, Terry; Silburn, Peter A.; Parker, John L.

    2015-12-01

    Objective. Deep brain stimulation (DBS) has become the standard treatment for advanced stages of Parkinson’s disease (PD) and other motor disorders. Although the surgical procedure has improved in accuracy over the years thanks to imaging and microelectrode recordings, the underlying principles that render DBS effective are still debated today. The aim of this paper is to present initial findings around a new biomarker that is capable of assessing the efficacy of DBS treatment for PD which could be used both as a research tool, as well as in the context of a closed-loop stimulator. Approach. We have used a novel multi-channel stimulator and recording device capable of measuring the response of nervous tissue to stimulation very close to the stimulus site with minimal latency, rejecting most of the stimulus artefact usually found with commercial devices. We have recorded and analyzed the responses obtained intraoperatively in two patients undergoing DBS surgery in the subthalamic nucleus (STN) for advanced PD. Main results. We have identified a biomarker in the responses of the STN to DBS. The responses can be analyzed in two parts, an initial evoked compound action potential arising directly after the stimulus onset, and late responses (LRs), taking the form of positive peaks, that follow the initial response. We have observed a morphological change in the LRs coinciding with a decrease in the rigidity of the patients. Significance. These initial results could lead to a better characterization of the DBS therapy, and the design of adaptive DBS algorithms that could significantly improve existing therapies and help us gain insights into the functioning of the basal ganglia and DBS.

  11. Effects of subthalamic nucleus deep brain stimulation and levodopa on energy production rate and substrate oxidation in Parkinson's disease.

    PubMed

    Perlemoine, Caroline; Macia, Frédéric; Tison, François; Coman, Isabelle; Guehl, Dominique; Burbaud, Pierre; Cuny, Emmanuel; Baillet, Laurence; Gin, Henri; Rigalleau, Vincent

    2005-02-01

    Patients with Parkinson's disease (PD) often lose weight, but after subthalamic nucleus deep brain stimulation (STN-DBS), they gain weight. We compared daily energy intake (DEI), resting energy expenditure (REE) and substrate oxidation rates (measured by indirect calorimetry) in nineteen STN-DBS-treated patients (Group S), thirteen others on pharmacologic treatment by levodopa (Group L) and eight control subjects. We also determined the acute effects of STN-DBS and levodopa on REE and substrate oxidation rates. STN-DBS treated patients gained 9.7 (SEM 7.1) kg after surgery, whereas patients on pharmacologic treatment lost 3.8 (SEM 10.0) kg since diagnosis. In STN-DBS-treated patients, REE (-16.5 %; P<0.001), lipid oxidation (-27 %; P<0.05) and protein oxidation (-46 %; P<0.05) were decreased, whereas glucose oxidation was elevated (+81 %; P<0.05) as compared to patients on pharmacologic treatment. Levodopa acutely reduced REE (-8.3 %; P<0.05) and glucose oxidation (-37 %; P<0.01) with a slight hyperglycaemic effect (after levodopa challenge: 5.6 (SEM 0.8) v. before levodopa challenge: 5.3 (SEM 0.6) mmol/l; P<0.01). Switching 'on' STN-DBS acutely reduced REE (-17.5 %; P<0.01) and lipid oxidation (-24 %; P<0.001) 30 min after starting stimulation. Fasting glycaemia was slightly but significantly reduced (5.4 (SEM 1.4) v. 5.5 (SEM 1.3) mmol/l; P<0.01). After STN-DBS, the normalization of REE and the reduction in lipid and protein oxidation contribute to the restoration of weight. As levodopa decreases glucose oxidation, the reduction in daily dose of levodopa in STN-DBS-treated patients helps prevent the effect of weight gain on glycaemia.

  12. Interleaving subthalamic nucleus deep brain stimulation to avoid side effects while achieving satisfactory motor benefits in Parkinson disease

    PubMed Central

    Zhang, Shizhen; Zhou, Peizhi; Jiang, Shu; Wang, Wei; Li, Peng

    2016-01-01

    Abstract Background: Deep brain stimulation (DBS) of the subthalamic nucleus is an effective treatment for advanced Parkinson disease (PD). However, achieving ideal outcomes by conventional programming can be difficult in some patients, resulting in suboptimal control of PD symptoms and stimulation-induced adverse effects. Interleaving stimulation (ILS) is a newer programming technique that can individually optimize the stimulation area, thereby improving control of PD symptoms while alleviating stimulation-induced side effects after conventional programming fails to achieve the desired results. Methods: We retrospectively reviewed PD patients who received DBS programming during the previous 4 years in our hospital. We collected clinical and demographic data from 12 patients who received ILS because of incomplete alleviation of PD symptoms or stimulation-induced adverse effects after conventional programming had proven ineffective or intolerable. Appropriate lead location was confirmed with postoperative reconstruction images. The rationale and clinical efficacy of ILS was analyzed. Results: We divided our patients into 4 groups based on the following symptoms: stimulation-induced dysarthria and choreoathetoid dyskinesias, gait disturbance, and incomplete control of parkinsonism. After treatment with ILS, patients showed satisfactory improvement in PD symptoms and alleviation of stimulation-induced side effects, with a mean improvement in Unified PD Rating Scale motor scores of 26.9%. Conclusions: ILS is a newer choice and effective programming strategy to maximize symptom control in PD while decreasing stimulation-induced adverse effects when conventional programming fails to achieve satisfactory outcome. However, we should keep in mind that most DBS patients are routinely treated with conventional stimulation and that not all patients benefit from ILS. ILS is not recommended as the first choice of programming, and it is recommended only when patients have

  13. [Discrepancy between imaging and neurophysiology in deep brain stimulation of medial pallidum and subthalamic nucleus in Parkinson's disease].

    PubMed

    Guridi, J; Rodríguez-Oroz, M C; Ramos, E; Linazasoro, G; Obeso, J A

    2002-04-01

    The objective of this work is to assess the discrepancy in distance between the target chosen by magnetic resonance imaging (MRI) and the final electrode placement after intraoperative microrecording in patients submitted to deep brain stimulation (DBS) for alleviating the Parkinson's disease (PD). Thirty patients with PD and motor complications were operated with stereotactic surgery by MRI and microrecording. In 19 patients, the target chosen was the subthalamic nucleus (STN) and in 11 others the target was globus pallidus internus (GPi). In this work it is considered that the electrode has a current field below usual parameters of 1.5 mm radius. Consequently, when the distance error between the final physiological target and the MRI target, is between 1.5 and 3 mm was considered as partial discrepancy and distances of 3 mm or more were considered as total discrepancy. Partial discrepancy for STN and GPi were in 25 and 33% of the cases respectively and total discrepancy was 57 and 42% for each nucleus. The average distance error between both targets, final and image, for X stereotactic coordinate (mediolateral distance) was 1.54 mm for STN and 0.8 mm for GPi. The average distance for Y coordinate (anteroposterior distance) was 2.3 mm for STN and 2.2 mm for GPi. There is a significant discrepancy between the final physiological target after microrecording and the target chosen by MRI during surgery for alleviating PD that may induce variations or absence of clinical efficacy in parkinsonian patients submitted to the DBS surgery. Authors suggest the necessity of the microelectrode recording in order to reach the surgical target with the best clinical condition.

  14. Subthalamic Nucleus Deep Brain Stimulation in Early Stage Parkinson’s Disease

    PubMed Central

    Charles, David; Konrad, Peter E.; Neimat, Joseph S.; Molinari, Anna L.; Tramontana, Michael G.; Finder, Stuart G.; Gill, Chandler E.; Bliton, Mark J.; Kao, Chris C.; Phibbs, Fenna T.; Hedera, Peter; Salomon, Ronald M.; Cannard, Kevin R.; Wang, Lily; Song, Yanna; Davis, Thomas L.

    2014-01-01

    Background Deep brain stimulation (DBS) is an effective and approved therapy for advanced Parkinson’s disease (PD), and a recent study suggests efficacy in mid-stage disease. This manuscript reports the results of a pilot trial investigating preliminary safety and tolerability of DBS in early PD. Methods Thirty subjects with idiopathic PD (Hoehn & Yahr Stage II off medication), age 50–75, on medication ≥ 6 months but < 4 years, and without motor fluctuations or dyskinesias were randomized to optimal drug therapy (ODT) (n=15) or DBS+ODT (n=15). Co-primary endpoints were the time to reach a 4-point worsening from baseline in the UPDRS-III off therapy and the change in levodopa equivalent daily dose from baseline to 24 months. Results As hypothesized, the mean UPDRS total and part III scores were not significantly different on or off therapy at 24 months. The DBS+ODT group took less medication at all time points, and this reached maximum difference at 18 months. With a few exceptions, differences in neuropsychological functioning were not significant. Two subjects in the DBS+ODT group suffered serious adverse events; remaining adverse events were mild or transient. Conclusions This study demonstrates that subjects with early stage PD will enroll in and complete trials testing invasive therapies and provides preliminary evidence that DBS is well tolerated in early PD. The results of this trial provide the data necessary to design a large, phase III, double-blind, multicenter trial investigating the safety and efficacy of DBS in early PD. PMID:24768120

  15. Meta-analysis comparing deep brain stimulation of the globus pallidus and subthalamic nucleus to treat advanced Parkinson disease.

    PubMed

    Liu, Yi; Li, Weina; Tan, Changhong; Liu, Xi; Wang, Xin; Gui, Yuejiang; Qin, Lu; Deng, Fen; Hu, Changlin; Chen, Lifen

    2014-09-01

    Deep brain stimulation (DBS) is the surgical procedure of choice for patients with advanced Parkinson disease (PD). The globus pallidus internus (GPi) and the subthalamic nucleus (STN) are commonly targeted by this procedure. The purpose of this meta-analysis was to compare the efficacy of DBS in each region. MEDLINE/PubMed, EMBASE, Web of Knowledge, and the Cochrane Library were searched for English-language studies published before April 2013. of studies investigating the efficacy and clinical outcomes of DBS of the GPi and STN for PD were analyzed. Six eligible trials containing a total of 563 patients were included in the analysis. Deep brain stimulation of the GPi or STN equally improved motor function, measured by the Unified Parkinson's Disease Rating Scale Section III (UPDRSIII) (motor section, for patients in on- and off-medication phases), within 1 year postsurgery. The change score for the on-medication phase was 0.68 (95% CI - 2.12 to 3.47, p > 0.05; 5 studies, 518 patients) and for the off-medication phase was 1.83 (95% CI - 3.12 to 6.77, p > 0.05; 5 studies, 518 patients). The UPDRS Section II (activities of daily living) scores for patients on medication improved equally in both DBS groups (p = 0.97). STN DBS allowed medication dosages to be reduced more than GPi DBS (95% CI 129.27-316.64, p < 0.00001; 5 studies, 540 patients). Psychiatric symptoms, measured by Beck Depression Inventory, 2nd edition scores, showed greater improvement from baseline after GPi DBS than after STN DBS (standardized mean difference -2.28, 95% CI -3.73 to -0.84, p = 0.002; 3 studies, 382 patients). GPi and STN DBS improve motor function and activities of daily living for PD patients. Differences in therapeutic efficacy for PD were not observed between the 2 procedures. STN DBS allowed greater reduction in medication for patients, whereas GPi DBS provided greater relief from psychiatric symptoms. An understanding of other symptomatic aspects of targeting each region and long

  16. Pilot study assessing the feasibility of applying bilateral subthalamic nucleus deep brain stimulation in very early stage Parkinson's disease: study design and rationale.

    PubMed

    Charles, David; Tolleson, Christopher; Davis, Thomas L; Gill, Chandler E; Molinari, Anna L; Bliton, Mark J; Tramontana, Michael G; Salomon, Ronald M; Kao, Chris; Wang, Lily; Hedera, Peter; Phibbs, Fenna T; Neimat, Joseph S; Konrad, Peter E

    2012-01-01

    Deep brain stimulation provides significant symptomatic benefit for people with advanced Parkinson's disease whose symptoms are no longer adequately controlled with medication. Preliminary evidence suggests that subthalamic nucleus stimulation may also be efficacious in early Parkinson's disease, and results of animal studies suggest that it may spare dopaminergic neurons in the substantia nigra. We report the methodology and design of a novel Phase I clinical trial testing the safety and tolerability of deep brain stimulation in early Parkinson's disease and discuss previous failed attempts at neuroprotection. We recently conducted a prospective, randomized, parallel-group, single-blind pilot clinical trial of deep brain stimulation in early Parkinson's disease. Subjects were randomized to receive either optimal drug therapy or deep brain stimulation plus optimal drug therapy. Follow-up visits occurred every six months for a period of two years and included week-long therapy washouts. Thirty subjects with Hoehn & Yahr Stage II idiopathic Parkinson's disease were enrolled over a period of 32 months. Twenty-nine subjects completed all follow-up visits; one patient in the optimal drug therapy group withdrew from the study after baseline. Baseline characteristics for all thirty patients were not significantly different. This study demonstrates that it is possible to recruit and retain subjects in a clinical trial testing deep brain stimulation in early Parkinson's disease. The results of this trial will be used to support the design of a Phase III, multicenter trial investigating the efficacy of deep brain stimulation in early Parkinson's disease.

  17. Subthalamic nucleus deep brain stimulation is neuroprotective in the A53T α‐synuclein Parkinson's disease rat model

    PubMed Central

    Musacchio, Thomas; Rebenstorff, Maike; Fluri, Felix; Brotchie, Jonathan M.; Volkmann, Jens; Koprich, James B.

    2017-01-01

    Objective Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a highly effective symptomatic therapy for motor deficits in Parkinson's disease (PD). An additional, disease‐modifying effect has been suspected from studies in toxin‐based PD animal models, but these models do not reflect the molecular pathology and progressive nature of PD that would be required to evaluate a disease‐modifying action. Defining a disease‐modifying effect could radically change the way in which DBS is used in PD. Methods We applied STN‐DBS in an adeno‐associated virus (AAV) 1/2‐driven human mutated A53T α‐synuclein (aSyn)‐overexpressing PD rat model (AAV1/2‐A53T‐aSyn). Rats were injected unilaterally, in the substantia nigra (SN), with AAV1/2‐A53T‐aSyn or control vector. Three weeks later, after behavioral and nigrostriatal dopaminergic deficits had developed, rats underwent STN‐DBS electrode implantation ipsilateral to the vector‐injected SN. Stimulation lasted for 3 weeks. Control groups remained OFF stimulation. Animals were sacrificed at 6 weeks. Results Motor performance in the single pellet reaching task was impaired in the AAV1/2‐A53T‐aSyn–injected stim‐OFF group, 6 weeks after AAV1/2‐A53T‐aSyn injection, compared to preoperative levels (–82%; p < 0.01). Deficits were reversed in AAV1/2‐A53T‐aSyn, stim‐ON rats after 3 weeks of active stimulation, compared to the AAV1/2‐A53T‐aSyn stim‐OFF rats (an increase of ∼400%; p < 0.05), demonstrating a beneficial effect of DBS. This motor improvement was maintained when the stimulation was turned off and was accompanied by a higher number of tyrosine hydroxylase+ SN neurons (increase of ∼29%), compared to AAV1/2‐A53T‐aSyn stim‐OFF rats (p < 0.05). Interpretation Our data support the putative neuroprotective and disease‐modifying effect of STN‐DBS in a mechanistically relevant model of PD. Ann Neurol 2017;81:825–836 PMID:28470693

  18. Neural Circuit Modulation During Deep Brain Stimulation at the Subthalamic Nucleus for Parkinson's Disease: What Have We Learned from Neuroimaging Studies?

    PubMed Central

    Albaugh, Daniel L.

    2014-01-01

    Abstract Deep brain stimulation (DBS) targeting the subthalamic nucleus (STN) represents a powerful clinical tool for the alleviation of many motor symptoms that are associated with Parkinson's disease. Despite its extensive use, the underlying therapeutic mechanisms of STN-DBS remain poorly understood. In the present review, we integrate and discuss recent literature examining the network effects of STN-DBS for Parkinson's disease, placing emphasis on neuroimaging findings, including functional magnetic resonance imaging, positron emission tomography, and single-photon emission computed tomography. These techniques enable the noninvasive detection of brain regions that are modulated by DBS on a whole-brain scale, representing a key experimental strength given the diffuse and far-reaching effects of electrical field stimulation. By examining these data in the context of multiple hypotheses of DBS action, generally developed through clinical and physiological observations, we define a multitude of consistencies and inconsistencies in the developing literature of this rapidly moving field. PMID:24147633

  19. Pilot Study Assessing the Feasibility of Applying Bilateral Subthalamic Nucleus Deep Brain Stimulation in Very Early Stage Parkinson's Disease: Study design and rationale

    PubMed Central

    Charles, David; Tolleson, Christopher; Davis, Thomas L.; Gill, Chandler E.; Molinari, Anna L.; Bliton, Mark J.; Tramontana, Michael G.; Salomon, Ronald M.; Kao, Chris; Wang, Lily; Hedera, Peter; Phibbs, Fenna T.; Neimat, Joseph S.; Konrad, Peter E.

    2014-01-01

    Background Deep brain stimulation provides significant symptomatic benefit for people with advanced Parkinson's disease whose symptoms are no longer adequately controlled with medication. Preliminary evidence suggests that subthalamic nucleus stimulation may also be efficacious in early Parkinson's disease, and results of animal studies suggest that it may spare dopaminergic neurons in the substantia nigra. Objective We report the methodology and design of a novel Phase I clinical trial testing the safety and tolerability of deep brain stimulation in early Parkinson's disease and discuss previous failed attempts at neuroprotection. Methods We recently conducted a prospective, randomized, parallel-group, single-blind pilot clinical trial of deep brain stimulation in early Parkinson's disease. Subjects were randomized to receive either optimal drug therapy or deep brain stimulation plus optimal drug therapy. Follow-up visits occurred every six months for a period of two years and included week-long therapy washouts. Results Thirty subjects with Hoehn & Yahr Stage II idiopathic Parkinson's disease were enrolled over a period of 32 months. Twenty-nine subjects completed all follow-up visits; one patient in the optimal drug therapy group withdrew from the study after baseline. Baseline characteristics for all thirty patients were not significantly different. Conclusions This study demonstrates that it is possible to recruit and retain subjects in a clinical trial testing deep brain stimulation in early Parkinson's disease. The results of this trial will be used to support the design of a Phase III, multicenter trial investigating the efficacy of deep brain stimulation in early Parkinson's disease. PMID:23938229

  20. Subthalamic nucleus-deep brain stimulation for early motor complications in Parkinson's disease-the EARLYSTIM trial: early is not always better.

    PubMed

    Mestre, Tiago A; Espay, Alberto J; Marras, Connie; Eckman, Mark H; Pollak, Pierre; Lang, Anthony E

    2014-12-01

    Subthalamic nucleus deep brain stimulation (STN-DBS) has revolutionized the management of disabling motor complications in Parkinson's disease. The EARLYSTIM trial applied this treatment to patients who had been experiencing motor complications for less than three years. STN-DBS significantly improved all primary and secondary outcome measures while best medical therapy failed to provide any improvement at the two-year follow-up time point. On face value these results strongly favor the application of STN-DBS far earlier than is currently applied, when patients are just beginning to experience problems with motor complications. Here we review the application of early DBS and the EARLYSTIM trial from the perspectives of clinical issues, health economics and study design and patient expectation of benefit. We conclude that the most relevant issue is not when to operate but on whom and that early is not always better. © 2014 International Parkinson and Movement Disorder Society.

  1. Deep Brain Stimulation of the Subthalamic Nucleus Alters Frontal Activity during Spatial Working Memory Maintenance of Patients with Parkinson’s Disease

    PubMed Central

    Mayer, Jutta S.; Neimat, Joseph; Folley, Bradley S.; Bourne, Sarah K.; Konrad, Peter E.; Charles, David; Park, Sohee

    2016-01-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves the motor symptoms of Parkinson’s disease (PD). The STN may represent an important relay station not only in the motor but also the associative cortico-striato-thalamocortical pathway. Therefore, STN stimulation may alter cognitive functions such as working memory (WM). We examined cortical effects of STN-DBS on WM in early PD patients using functional near-infrared spectroscopy. The effects of dopaminergic medication on WM were also examined. Lateral frontal activity during WM maintenance was greater when patients were taking dopaminergic medication. STN-DBS led to a trend-level worsening of WM performance, accompanied by increased lateral frontal activity during WM maintenance. These findings suggest that STN-DBS in PD might lead to functional modifications of the basal ganglia-thalamocortical pathway during WM maintenance. PMID:27337498

  2. Bilateral subthalamic nucleus deep brain stimulation for refractory total body dystonia secondary to metabolic autopallidotomy in a 4-year-old boy with infantile methylmalonic acidemia: case report.

    PubMed

    Chakraborti, Santo; Hasegawa, Harutomo; Lumsden, Daniel E; Ali, Wisam; Kaminska, Margaret; Lin, Jean-Pierre; Ashkan, Keyoumars

    2013-10-01

    The methylmalonic acidemias (MMAs) are a group of inborn errors of metabolism resulting in the accumulation of methylmalonic acid in body tissues and fluids. A recognized complication of MMA is bilateral liquefaction of the globus pallidi, resulting in a fulminant total body dystonia of childhood often refractory to medical treatment. This case of total body dystonia due to MMA in a 4-year-old boy had been medically refractory for 15 months. Complete metabolic destructive liquefaction of the pallidi, that is, autopallidotomy, necessitated an alternative, bilateral subthalamic nucleus (STN) target for deep brain stimulation (DBS) with a marked improvement in dystonia and reduction in pain. The case illustrates the efficacy of STN DBS in this condition and the technical challenges in targeting the STN in a small child.

  3. The organization of prefrontal-subthalamic inputs in primates provides an anatomical substrate for both functional specificity and integration: implications for basal ganglia models and deep brain stimulation

    PubMed Central

    Haynes, William I. A.; Haber, Suzanne N.

    2013-01-01

    The identification of a hyperdirect cortico-subthalamic nucleus connection highlighted the important role of the subthalamic nucleus (STN) in regulating behavior. However, this pathway was shown primarily from motor areas. Hyperdirect pathways associated with cognitive and motivational cortical regions are particularly relevant given recent data from deep brain stimulation, both for neurological and psychiatric disorders. Our experiments were designed to: demonstrate the existence and organization of prefrontal-STN projections, help delineate the ‘limbic’ STN, and determine whether convergence between cortico-STN fibers from functionally diverse cortical areas exists in the STN. We injected anterograde tracers in the ventromedial prefrontal, orbitofrontal, anterior cingulate and dorsal prefrontal cortices of Macaca nemestrina & M. fascicularis to analyze the organization of terminals and passing fibers in the STN. Results show a topographically organized prefrontal hyperdirect pathway in primates. Limbic areas project to the medial tip of the nucleus, straddling its border and extending into the lateral hypothalamus. Associative areas project to the medial half, motor areas to the lateral half. Limbic projections terminated primarily rostrally and motor projections more caudally. The extension of limbic projections into the lateral hypothalamus, suggests that this region be included in the STN. A high degree of convergence exists between projections from functionally diverse cortical areas, creating potentially important interfaces between terminal fields. Taken together, the results provide an anatomical substrate to extend the role of the hyperdirect pathway in models of basal ganglia function, and new keys for understanding deep brain stimulation effects on cognitive and motivational aspects of behavior. PMID:23486951

  4. Statistical Power of Studies Examining the Cognitive Effects of Subthalamic Nucleaus Deep Brain Stimulation in Parkinson’s Disease

    DTIC Science & Technology

    2006-01-01

    bilateral subthalamic nucleus stimulation in Parkinson’s disease. Archives of Clinical Neuropsychology , 19, 165–181. 36 STEVEN PAUL WOODS ET AL. Patel...Formulae, illustrative numerical examples, and heuristic interpretation of effect size analyses for neuropsychological researchers. Archives of Clinical Neuropsychology , 16, 653–667. 38 STEVEN PAUL WOODS ET AL.

  5. Cortical Plasticity Induction by Pairing Subthalamic Nucleus Deep-Brain Stimulation and Primary Motor Cortical Transcranial Magnetic Stimulation in Parkinson's Disease.

    PubMed

    Udupa, Kaviraja; Bahl, Nina; Ni, Zhen; Gunraj, Carolyn; Mazzella, Filomena; Moro, Elena; Hodaie, Mojgan; Lozano, Andres M; Lang, Anthony E; Chen, Robert

    2016-01-13

    Noninvasive brain stimulation studies have shown abnormal motor cortical plasticity in Parkinson's disease (PD). These studies used peripheral nerve stimulation paired with transcranial magnetic stimulation (TMS) to primary motor cortex (M1) at specific intervals to induce plasticity. Induction of cortical plasticity through stimulation of the basal ganglia (BG)-M1 connections has not been studied. In the present study, we used a novel technique of plasticity induction by repeated pairing of deep-brain stimulation (DBS) of the BG with M1 stimulation using TMS. We hypothesize that repeated pairing of subthalamic nucleus (STN)-DBS and M1-TMS at specific time intervals will lead to plasticity in the M1. Ten PD human patients with STN-DBS were studied in the on-medication state with DBS set to 3 Hz. The interstimulus intervals (ISIs) between STN-DBS and TMS that produced cortical facilitation were determined individually for each patient. Three plasticity induction conditions with repeated pairings (180 times) at specific ISIs (∼ 3 and ∼ 23 ms) that produced cortical facilitation and a control ISI of 167 ms were tested in random order. Repeated pairing of STN-DBS and M1-TMS at short (∼ 3 ms) and medium (∼ 23 ms) latencies increased M1 excitability that lasted for at least 45 min, whereas the control condition (fixed ISI of 167 ms) had no effect. There were no specific changes in motor thresholds, intracortical circuits, or recruitment curves. Our results indicate that paired-associative cortical plasticity can be induced by repeated STN and M1 stimulation at specific intervals. These results show that STN-DBS can modulate cortical plasticity. We introduced a new experimental paradigm to test the hypothesis that pairing subthalamic nucleus deep-brain stimulation (STN-DBS) with motor cortical transcranial magnetic stimulation (M1-TMS) at specific times can induce cortical plasticity in patients with Parkinson's disease (PD). We found that repeated pairing of STN

  6. Deep brain stimulation of the subthalamic nucleus alters the cortical profile of response inhibition in the beta frequency band: a scalp EEG study in Parkinson's disease

    PubMed Central

    Swann, Nicole; Poizner, Howard; Houser, Melissa; Gould, Sherrie; Greenhouse, Ian; Cai, Weidong; Strunk, Jon; George, Jobi; Aron, Adam R

    2011-01-01

    Stopping an initiated response could be implemented by a fronto-basal-ganglia circuit, including the right inferior frontal cortex (rIFC) and the subthalamic nucleus (STN). Intracranial recording studies in humans reveal an increase in beta-band power (~16-20 Hz) within the rIFC and STN when a response is stopped. This suggests that the beta-band could be important for communication in this network. If this is the case, then altering one region should affect the electrophysiological response at the other. We addressed this hypothesis by recording scalp EEG during a stop task while modulating STN activity with deep brain stimulation. We studied 15 human patients with Parkinson's Disease and 15 matched healthy control subjects. Behaviorally, patients OFF stimulation were slower than controls to stop their response. Moreover, stopping speed was improved for ON compared to OFF stimulation. For scalp EEG, there was greater beta power, around the time of stopping, for patients ON compared to OFF stimulation. This effect was stronger over the right compared to left frontal cortex, consistent with the putative right-lateralization of the stopping network. Thus, deep brain stimulation of the STN improved behavioral stopping performance and increased the beta-band response over the right frontal cortex. These results complement other evidence for a structurally-connected, functional, circuit between right frontal cortex and the basal ganglia. The results also suggest that deep brain stimulation of the STN may improve task performance by increasing the fidelity of information transfer within a fronto-basal ganglia circuit. PMID:21490213

  7. Subthalamic Nucleus Deep Brain Stimulation Modulate Catecholamine Levels with Significant Relations to Clinical Outcome after Surgery in Patients with Parkinson’s Disease

    PubMed Central

    Yamamoto, Tatsuya; Uchiyama, Tomoyuki; Higuchi, Yoshinori; Asahina, Masato; Hirano, Shigeki; Yamanaka, Yoshitaka; Kuwabara, Satoshi

    2015-01-01

    Aims Although subthalamic nucleus deep brain stimulation (STN-DBS) is effective in patients with advanced Parkinson’s disease (PD), its physiological mechanisms remain unclear. Because STN-DBS is effective in patients with PD whose motor symptoms are dramatically alleviated by L-3,4-dihydroxyphenylalanine (L-DOPA) treatment, the higher preoperative catecholamine levels might be related to the better clinical outcome after surgery. We aimed to examine the correlation between the preoperative catecholamine levels and postoperative clinical outcome after subthalamic nucleus deep brain stimulation. The effectiveness of STN-DBS in the patient who responded well to dopaminergic medication suggest the causal link between the dopaminergic system and STN-DBS. We also examined how catecholamine levels were modulated after subthalamic stimulation. Methods In total 25 patients with PD were enrolled (Mean age 66.2 ± 6.7 years, mean disease duration 11.6 ± 3.7 years). Mean levodopa equivalent doses were 1032 ± 34.6 mg before surgery. Cerebrospinal fluid and plasma catecholamine levels were measured an hour after oral administration of antiparkinsonian drugs before surgery. The mean Unified Parkinson’s Disease Rating Scale scores (UPDRS) and the Parkinson’s disease Questionnaire-39 (PDQ-39) were obtained before and after surgery. Of the 25 patients, postoperative cerebrospinal fluid and plasma were collected an hour after oral administration of antiparkinsonian drugs during on stimulation at follow up in 11 patients. Results Mean levodopa equivalent doses significantly decreased after surgery with improvement in motor functions and quality of life. The preoperative catecholamine levels had basically negative correlations with postoperative motor scores and quality of life, suggesting that higher preoperative catecholamine levels were related to better outcome after STN-DBS. The preoperative plasma levels of L-DOPA had significantly negative correlations with

  8. Microelectrode Guided Implantation of Electrodes into the Subthalamic Nucleus of Rats for Long-term Deep Brain Stimulation

    PubMed Central

    Fluri, Felix; Bieber, Micheal; Volkmann, Jens; Kleinschnitz, Christoph

    2015-01-01

    Deep brain stimulation (DBS) is a widely used and effective therapy for several neurologic disorders, such as idiopathic Parkinson’s disease, dystonia or tremor. DBS is based on the delivery of electrical stimuli to specific deep anatomic structures of the central nervous system. However, the mechanisms underlying the effect of DBS remain enigmatic. This has led to an interest in investigating the impact of DBS in animal models, especially in rats. As DBS is a long-term therapy, research should be focused on molecular-genetic changes of neural circuits that occur several weeks after DBS. Long-term DBS in rats is challenging because the rats move around in their cage, which causes problems in keeping in place the wire leading from the head of the animal to the stimulator. Furthermore, target structures for stimulation in the rat brain are small and therefore electrodes cannot easily be placed at the required position. Thus, a set-up for long-lasting stimulation of rats using platinum/iridium electrodes with an impedance of about 1 MΩ was developed for this study. An electrode with these specifications allows for not only adequate stimulation but also recording of deep brain structures to identify the target area for DBS. In our set-up, an electrode with a plug for the wire was embedded in dental cement with four anchoring screws secured onto the skull. The wire from the plug to the stimulator was protected by a stainless-steel spring. A swivel was connected to the circuit to prevent the wire from becoming tangled. Overall, this stimulation set-up offers a high degree of free mobility for the rat and enables the head plug, as well as the wire connection between the plug and the stimulator, to retain long-lasting strength. PMID:26485522

  9. Increase in body weight is a non-motor side effect of deep brain stimulation of the subthalamic nucleus in Parkinson's disease.

    PubMed

    Novakova, Lucie; Ruzicka, Evzen; Jech, Robert; Serranova, Tereza; Dusek, Petr; Urgosik, Dusan

    2007-02-01

    Deep brain stimulation of the subthalamic nucleus (DBS STN) is an effective treatment method in advanced Parkinson's disease (PD) providing marked improvement of its major motor symptoms. In addition, non-motor effects have been reported including weight gain in PD patients after DBS STN. Using retrospective survey, we aimed to evaluate weight changes in our patients with advanced PD treated with DBS STN. We inquired 25 PD patients (16 men, 9 women), of mean age 55 (42-65) years, mean PD duration 15 (9-21) years, who previously received bilateral DBS STN. We obtained valid data from 23 patients. In the first survey, 1 to 45 months after DBS, weight gain was found in all patients comparing to pre-DBS period. The mean increase was 9.4 kg (from 1 to 25 kg). The patients' mean body mass index (BMI) increased from 23.7 to 27.0 kg/m2, i.e. by 3.3 kg/m2 (+2 to +6.1 kg/m2). In the repeated survey one year later, in 12 of the patients body weight moderately decreased, 3 did not change, and 6 patients further increased their weight. Possible explanations of body weight gain after DBS STN include a reduction of energy output related to elimination of dyskinesias, improved alimentation or direct influence on function of lateral hypothalamus by DBS STN.

  10. Are Two Leads Always Better Than One: An Emerging Case for Unilateral Subthalamic Deep Brain Stimulation in Parkinson’s disease

    PubMed Central

    Alberts, J. L.; Hass, C.J.; Vitek, J. L.; Okun, M.S.

    2008-01-01

    Bilateral subthalamic (STN) deep brain stimulation (DBS) provides significant symptom relief for the majority of well-screened patients suffering with Parkinson’s disease (PD). Implantation of stimulating electrodes bilaterally in a single session has become standard in most operating theaters worldwide. There is, however, limited evidence-based support for this approach. Although bilateral surgical procedures have been shown, using standardized clinical ratings, to provide greater motor benefits compared to unilateral procedures, bilateral procedures are more likely to be associated with increased acute and long- term complications including post-operative confusion, speech difficulties and cognitive dysfunction. Unilateral stimulation has been shown to provide significant benefits for appendicular and axial symptoms. The relative benefit of implanting one versus two sides and whether the degree of benefit associated with the second side is worth the potential risk of doing so have not been examined systematically. The relative magnitude of benefit associated with unilateral versus bilateral procedures is likely to vary from patient to patient, particularly in those patients with asymmetric symptomatology. As such, there are likely subsets of patients who do not require and therefore should not be exposed to the potential complications associated with bilateral simultaneous implantation. This review and commentary will outline our current understanding of the benefits associated with unilateral and bilateral STN DBS and discuss the role of unilateral or staged unilateral procedures as an alternative surgical approach for patients with advanced PD. PMID:18718469

  11. Deep brain stimulation of the pedunculopontine tegmental nucleus modulates neuronal hyperactivity and enhanced beta oscillatory activity of the subthalamic nucleus in the rat 6-hydroxydopamine model.

    PubMed

    Alam, Mesbah; Heissler, Hans E; Schwabe, Kerstin; Krauss, Joachim K

    2012-01-01

    Deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) area has been introduced as a novel surgical therapy for dopamine refractory gait problems, freezing and postural instability in the late stage of Parkinson's disease (PD). Lesions of the pedunculopontine tegmental (PPTg) nucleus, the equivalent of the PPN in rodents, were shown to reduce the elevated discharge rate of the subthalamic nucleus (STN) in the 6-hydroxydopamine (6-OHDA) rat model of PD. In order to further elucidate the modulatory effect of the PPTg on the STN we examined the effect of 25 Hz low frequency PPTg stimulation on neuronal single unit activity and oscillatory local field potentials (LFPs) of the STN, and on the electrocorticogram (ECoG) of the primary motor cortex region in rats with unilateral 6-OHDA induced nigrostriatal lesions. Stimulation of the PPTg reduced the enhanced firing rate in the STN, without affecting the firing pattern or approximate entropy (ApEn). It also reduced the activity in the beta band (15-30 Hz) of the STN, which is elevated in 6-OHDA lesioned rats, without affecting beta activity in the motor cortex. We showed a modulatory effect of PPTg stimulation on altered neuronal STN activity in the PD 6-OHDA rat model, indicating that PPTg DBS may alter activity of the basal ganglia circuitry at least partially. It remains unclear, however, how these changes are exactly mediated and whether they are relevant with regard to the descending PPTg projections in the lower brainstem.

  12. Effects of different electrical parameter settings on the intelligibility of speech in patients with Parkinson's disease treated with subthalamic deep brain stimulation.

    PubMed

    Törnqvist, Anna Lena; Schalén, Lucyna; Rehncrona, Stig

    2005-04-01

    We evaluated the effects of different electrical parameter settings on the intelligibility of speech in patients with Parkinson's disease (PD) bilaterally treated with deep brain stimulation (DBS) in the subthalamic nucleus (STN). Ten patients treated with DBS for 15 +/- 5 months (mean, SD) with significant (P < 0.01) symptom reduction (Unified Parkinson's Disease Rating Scale III) were included. In the medication off condition, video laryngostroboscopy was performed and then, in random order, 11 DBS parameter settings were tested. Amplitude was increased and decreased by 25%, frequency was varied in the range 70 to 185 pps, and each of the contacts was tested separately as a cathode. The patients read a standard running text and five nonsense sentences per setting. A listener panel transcribed the nonsense sentences as perceived and valued the quality of speech on a visual analogue scale. With the patients' normally used settings, there was no significant (P = 0.058) group difference between DBS OFF and ON, but in four patients the intelligibility deteriorated with DBS ON. The higher frequencies or increased amplitude caused significant (P < 0.02) impairments of intelligibility, whereas changing the polarity between the separate contacts did not. The settings of amplitude and frequency have a major influence on the intelligibility of speech, emphasizing the importance of meticulous parameter adjustments when programming DBS to minimize side effects related to speech.

  13. Hemisphere-Specific Effects of Subthalamic Nucleus Deep Brain Stimulation on Speaking Rate and Articulatory Accuracy of Syllable Repetitions in Parkinson's Disease.

    PubMed

    Wang, Emily Q; Metman, Leo Verhagen; Bakay, Roy A E; Arzbaecher, Jean; Bernard, Bryan; Corcos, Daniel M

    2006-01-01

    This study tested the hypothesis that left versus right deep brain stimulation (DBS) of the subthalamic nucleus (STN) would have differential effects on speech. Twenty right-handed individuals with advanced Parkinson's disease (PD) underwent unilateral STN DBS. Ten were operated on the right and 10 on the left hemisphere as indicated by severity of nonspeech motor function. Speech was evaluated before surgery and 3 to 6 months after surgery with stimulator-off and with stimulator-on, with all participants off anti-parkinsonian medication for 12 hours before evaluation. Evaluators and patient speakers were blinded to the stimulator status at the postsurgery evaluations. Motor performance was assessed with UPDRS-III. Each participant produced three samples of diadochokinetic syllables. Syllable rate, syllable and vowel duration, VOT, and F0 were obtained. The diadochokinetic syllables were rated for articulatory accuracy and speaking rate. Twenty graduate clinicians served as judges. The samples were randomly presented via headphones. A mixed ANOVA with repeated measures was used to assess the significance of the changes in UPRS-III scores and speech measures. The results indicated that unilateral STN DBS produced improvement in nonspeech motor function regardless of the side of stimulation. In contrast, the changes in articulatory accuracy and syllable rate associated with the STN DBS were hemisphere specific.

  14. Effects of medication and subthalamic nucleus deep brain stimulation on tongue movements in speakers with Parkinson's disease using electropalatography: a pilot study.

    PubMed

    Hartinger, Mariam; Tripoliti, Elina; Hardcastle, William J; Limousin, Patricia

    2011-03-01

    Parkinson's disease (PD) affects speech in the majority of patients. Subthalamic nucleus deep brain stimulation (STN-DBS) is particularly effective in reducing tremor and rigidity. However, its effect on speech is variable. The aim of this pilot study was to quantify the effects of bilateral STN-DBS and medication on articulation, using electropalatography (EPG). Two patients, PT1 and PT2, were studied under four conditions: on and off medication and ON and OFF stimulation. The EPG protocol consisted of a number of target words with alveolar and velar stops, repeated 10 times in random order. The motor part III of the Unified Parkinson Disease Rating Scale (UPDRS) indicated significantly improved motor scores in the ON stimulation condition in both patients. However, PT1's articulation patterns deteriorated with stimulation whereas PT2 showed improving articulatory accuracy in the same condition. The results revealed different effects of stimulation and medication on articulation particularly with regard to timing. The study quantified less articulatory undershoot for velar stops in comparison to alveolars. Furthermore, the findings provided preliminary evidence that stimulation with medication has a more detrimental effect on articulation than stimulation without medication.

  15. Dominant efficiency of nonregular patterns of subthalamic nucleus deep brain stimulation for Parkinson’s disease and obsessive-compulsive disorder in a data-driven computational model

    NASA Astrophysics Data System (ADS)

    Karamintziou, Sofia D.; Deligiannis, Nick G.; Piallat, Brigitte; Polosan, Mircea; Chabardès, Stephan; David, Olivier; Stathis, Pantelis G.; Tagaris, George A.; Boviatsis, Efstathios J.; Sakas, Damianos E.; Polychronaki, Georgia E.; Tsirogiannis, George L.; Nikita, Konstantina S.

    2016-02-01

    Objective. Almost 30 years after the start of the modern era of deep brain stimulation (DBS), the subthalamic nucleus (STN) still constitutes a standard stimulation target for advanced Parkinson’s disease (PD), but the use of STN-DBS is also now supported by level I clinical evidence for treatment-refractory obsessive-compulsive disorder (OCD). Disruption of neural synchronization in the STN has been suggested as one of the possible mechanisms of action of standard and alternative patterns of STN-DBS at a local level. Meanwhile, recent experimental and computational modeling evidence has signified the efficiency of alternative patterns of stimulation; however, no indications exist for treatment-refractory OCD. Here, we comparatively simulate the desynchronizing effect of standard (regular at 130 Hz) versus temporally alternative (in terms of frequency, temporal variability and the existence of bursts or pauses) patterns of STN-DBS for PD and OCD, by means of a stochastic dynamical model and two microelectrode recording (MER) datasets. Approach. The stochastic model is fitted to subthalamic MERs acquired during eight surgical interventions for PD and eight surgical interventions for OCD. For each dynamical system simulated, we comparatively assess the invariant density (steady-state phase distribution) as a measure inversely related to the desynchronizing effect yielded by the applied patterns of stimulation. Main results. We demonstrate that high (130 Hz)—and low (80 Hz)—frequency irregular patterns of stimulation, and low-frequency periodic stimulation interrupted by bursts of pulses, yield in both pathologic conditions a significantly stronger desynchronizing effect compared with standard STN-DBS, and distinct alternative patterns of stimulation. In PD, values of the invariant density measure are proven to be optimal at the dorsolateral oscillatory region of the STN including sites with the optimal therapeutic window. Significance. In addition to providing

  16. Dominant efficiency of nonregular patterns of subthalamic nucleus deep brain stimulation for Parkinson's disease and obsessive-compulsive disorder in a data-driven computational model.

    PubMed

    Karamintziou, Sofia D; Deligiannis, Nick G; Piallat, Brigitte; Polosan, Mircea; Chabardès, Stephan; David, Olivier; Stathis, Pantelis G; Tagaris, George A; Boviatsis, Efstathios J; Sakas, Damianos E; Polychronaki, Georgia E; Tsirogiannis, George L; Nikita, Konstantina S

    2016-02-01

    Almost 30 years after the start of the modern era of deep brain stimulation (DBS), the subthalamic nucleus (STN) still constitutes a standard stimulation target for advanced Parkinson's disease (PD), but the use of STN-DBS is also now supported by level I clinical evidence for treatment-refractory obsessive-compulsive disorder (OCD). Disruption of neural synchronization in the STN has been suggested as one of the possible mechanisms of action of standard and alternative patterns of STN-DBS at a local level. Meanwhile, recent experimental and computational modeling evidence has signified the efficiency of alternative patterns of stimulation; however, no indications exist for treatment-refractory OCD. Here, we comparatively simulate the desynchronizing effect of standard (regular at 130 Hz) versus temporally alternative (in terms of frequency, temporal variability and the existence of bursts or pauses) patterns of STN-DBS for PD and OCD, by means of a stochastic dynamical model and two microelectrode recording (MER) datasets. The stochastic model is fitted to subthalamic MERs acquired during eight surgical interventions for PD and eight surgical interventions for OCD. For each dynamical system simulated, we comparatively assess the invariant density (steady-state phase distribution) as a measure inversely related to the desynchronizing effect yielded by the applied patterns of stimulation. We demonstrate that high (130 Hz)-and low (80 Hz)-frequency irregular patterns of stimulation, and low-frequency periodic stimulation interrupted by bursts of pulses, yield in both pathologic conditions a significantly stronger desynchronizing effect compared with standard STN-DBS, and distinct alternative patterns of stimulation. In PD, values of the invariant density measure are proven to be optimal at the dorsolateral oscillatory region of the STN including sites with the optimal therapeutic window. In addition to providing novel insights into the efficiency of low

  17. Remotely Programmed Deep Brain Stimulation of the Bilateral Subthalamic Nucleus for the Treatment of Primary Parkinson Disease: A Randomized Controlled Trial Investigating the Safety and Efficacy of a Novel Deep Brain Stimulation System.

    PubMed

    Li, Dianyou; Zhang, Chencheng; Gault, Judith; Wang, Wei; Liu, Jianmin; Shao, Ming; Zhao, Yanyan; Zeljic, Kristina; Gao, Guodong; Sun, Bomin

    2017-01-01

    Deep brain stimulation (DBS) is the most commonly performed surgery for the debilitating symptoms of Parkinson disease (PD). However, DBS systems remain largely unaffordable to patients in developing countries, warranting the development of a safe, economically viable, and functionally comparable alternative. To investigate the efficacy and safety of wirelessly programmed DBS of bilateral subthalamic nucleus (STN) in patients with primary PD. Sixty-four patients with primary PD were randomly divided into test and control groups (1:1), where DBS was initiated at either 1 month or 3 months, respectively, after surgery. Safety and efficacy of the treatment were compared between on- and off-medication states 3 months after surgery. Outcome measures included analysis of Unified Parkinson's Disease Rating Scale (UPDRS) scores, duration of "on" periods, and daily equivalent doses of levodopa. All patients were followed up both 6 and 12 months after surgery. Three months after surgery, significant decrease in the UPDRS motor scores were observed for the test group in the off-medication state (25.08 ± 1.00) versus the control group (4.20 ± 1.99). Bilateral wireless programming STN-DBS is safe and effective for patients with primary PD in whom medical management has failed to restore motor function. © 2017 S. Karger AG, Basel.

  18. Betting on DBS: Effects of Subthalamic Nucleus Deep Brain Stimulation on Risk-Taking and Decision-Making in Patients with Parkinson’s Disease

    PubMed Central

    Brandt, Jason; Rogerson, Mark; Al-Joudi, Haya; Reckess, Gila; Shpritz, Barnett; Umeh, Chizoba C.; Aljehani, Noha; Mills, Kelly; Mari, Zoltan

    2014-01-01

    Objective Concerns persist that deep brain stimulation (DBS) for Parkinson’s disease (PD) increases impulsivity and/or induces excessive reward-seeking. We report here the performance of PD patients with implanted subthalamic nucleus electrodes, with stimulation on and off, on three laboratory tasks of risk-taking and decision-making. They are compared to PD patients maintained on medication and normal control subjects. Methods and Results In the Game of Dice Task, a test of “risky” decision-making, PD patients with or without DBS made highest-risk bets more often, and ended up with less money, than normal controls. There was a trend for DBS stimulation to ameliorate this effect. Deal or No-Deal is an “ambiguous” decision-making task that assessed preference for risk (holding on to one’s briefcase) over a “sure thing” (accepting the banker’s offer). Here, DBS patients were more conservative with stimulation on than off. They accepted smaller offers from the banker and won less money in the DBS-on condition. Overall, the two PD groups won less money than healthy participants. The Framing Paradigm assessed willingness to gamble on a fixed (unambiguous) prize depending on whether the reward was “framed” as a loss or a gain. Nonsurgical PD patients tended to be more risk-averse than normal subjects, whereas DBS patients were more willing to gamble for gains as well as losses both on and off stimulation. Conclusions On “risky” decision-making tasks, DBS patients were more risk-taking than normal, but stimulation may temper this tendency. In contrast, in an “ambiguous risk” situation, DBS patients were more risk-averse (conservative) than normal, and this tendency was greatest with stimulation. PMID:25486385

  19. Subthalamic Nucleus Deep Brain Stimulation for Parkinson Disease in Hong Kong: A Prospective Territory-Wide 2-Year Follow-Up Study.

    PubMed

    Chan, Danny T M; Zhu, Cannon X L; Lau, Claire K Y; Poon, Tak L; Cheung, Fung C; Lee, Michael; Taw, Benedict; Hung, Kwan N; Choi, Priscilla; AuYeung, Mandy; Chan, Germaine; Cheung, Yuk F; Chan, Anne Y Y; Yeung, Jonas H M; Mok, Vincent C T; Poon, Wai S

    2016-09-01

    We assessed the effects of bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) in patients with Parkinson disease at the 1-year and 2-year follow-up evaluations. Unified Parkinson's Disease Rating Scale (UPDRS) motor score at "off" medication ("on" DBS) and quality-of-life assessments (39-item Parkinson's Disease Questionnaire [PDQ-39]) were conducted. The percentage of awake "on" time and awake "off" time and levodopa requirement were also assessed. A 2-year prospective study was conducted of 25 consecutive patients from 3 DBS referral centers in Hong Kong. The patients were treated with bilateral stimulation of the STN. Assessments were performed at 1 year and 2 years after DBS and were compared with the baseline. The 2-year outcome assessments were completed by 18 patients. The mean UPDRS motor score improvement was 57% in the first year and 45% in the second year. PDQ-39 showed significant improvement in quality of life for 2 consecutive years. The levodopa requirement decreased 63% in the first year and 55.9% in the second year. The awake "on" time was doubled in the first year and sustained in the second year. Awake "off" time was reduced from 28.1% to 5.9% in the first year and returned to 10.6% in the second year. Improvement of UPDRS motor score, reduction in awake "off" time, and decrease of daily levodopa dosage all were main factors correlated with the improvement in PDQ-39 summary index. The effects of STN DBS in patients with Parkinson disease in Hong Kong were satisfactory. The results showed that reduction in UPDRS motor score, awake "off"-time, and daily levodopa dosage were the major drivers of overall improvement in PDQ-39. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Load-Dependent Interference of Deep Brain Stimulation of the Subthalamic Nucleus with Switching from Automatic to Controlled Processing During Random Number Generation in Parkinson's Disease.

    PubMed

    Williams, Isobel Anne; Wilkinson, Leonora; Limousin, Patricia; Jahanshahi, Marjan

    2015-01-01

    Deep brain stimulation of the subthalamic nucleus (STN DBS) ameliorates the motor symptoms of Parkinson's disease (PD). However, some aspects of executive control are impaired with STN DBS. We tested the prediction that (i) STN DBS interferes with switching from automatic to controlled processing during fast-paced random number generation (RNG) (ii) STN DBS-induced cognitive control changes are load-dependent. Fifteen PD patients with bilateral STN DBS performed paced-RNG, under three levels of cognitive load synchronised with a pacing stimulus presented at 1, 0.5 and 0.33 Hz (faster rates require greater cognitive control), with DBS on or off. Measures of output randomness were calculated. Countscore 1 (CS1) indicates habitual counting in steps of one (CS1). Countscore 2 (CS2) indicates a more controlled strategy of counting in twos. The fastest rate was associated with an increased CS1 score with STN DBS on compared to off. At the slowest rate, patients had higher CS2 scores with DBS off than on, such that the differences between CS1 and CS2 scores disappeared. We provide evidence for a load-dependent effect of STN DBS on paced RNG in PD. Patients could switch to more controlled RNG strategies during conditions of low cognitive load at slower rates only when the STN stimulators were off, but when STN stimulation was on, they engaged in more automatic habitual counting under increased cognitive load. These findings are consistent with the proposal that the STN implements a switch signal from the medial frontal cortex which enables a shift from automatic to controlled processing.

  1. In Parkinson's disease on a probabilistic Go/NoGo task deep brain stimulation of the subthalamic nucleus only interferes with withholding of the most prepotent responses.

    PubMed

    Georgiev, Dejan; Dirnberger, Georg; Wilkinson, Leonora; Limousin, Patricia; Jahanshahi, Marjan

    2016-04-01

    The evidence on the impact of subthalamic nucleus deep brain stimulation (STN-DBS) on action restraint on Go/NoGO reaction time (RT) tasks in Parkinson's disease (PD) is inconsistent; with some studies reporting no effect and others finding that STN stimulation interferes with withholding of responses and results in more commission errors relative to STN-DBS off. We used a task in which the probability of Go stimuli varied from 100% (simple RT task) to 80, 50 and 20% (probabilistic Go/NoGo RT task), thus altering the prepotency of the response and the difficulty in withholding it on NoGo trials. Twenty PD patients with STN-DBS, ten unoperated PD patients and ten healthy controls participated in the study. All participants were tested twice; the order of on versus off stimulation for STN-DBS PD patients was counterbalanced. Both STN-DBS and unoperated PD patients were tested on medication. The results indicated that STN-DBS selectively decreased discriminability when the response was most prepotent (high--80%, as compared to low Go probability trials--50 and 20%). Movement times were faster with STN stimulation than with DBS off across different Go probability levels. There was neither an overall nor a selective effect of STN-DBS on RTs depending on the level of Go probability. Furthermore, compared to healthy controls, both STN-DBS and unoperated PD patients were more prone to making anticipatory errors; which was not influenced by STN stimulation. The results provide evidence for 'load-dependent' effects of STN stimulation on action restraint as a function of the prepotency of the Go response.

  2. Predictive timing functions of cortical beta oscillations are impaired in Parkinson's disease and influenced by L-DOPA and deep brain stimulation of the subthalamic nucleus

    PubMed Central

    Gulberti, A.; Moll, C.K.E.; Hamel, W.; Buhmann, C.; Koeppen, J.A.; Boelmans, K.; Zittel, S.; Gerloff, C.; Westphal, M.; Schneider, T.R.; Engel, A.K.

    2015-01-01

    Cortex-basal ganglia circuits participate in motor timing and temporal perception, and are important for the dynamic configuration of sensorimotor networks in response to exogenous demands. In Parkinson's disease (PD) patients, rhythmic auditory stimulation (RAS) induces motor performance benefits. Hitherto, little is known concerning contributions of the basal ganglia to sensory facilitation and cortical responses to RAS in PD. Therefore, we conducted an EEG study in 12 PD patients before and after surgery for subthalamic nucleus deep brain stimulation (STN-DBS) and in 12 age-matched controls. Here we investigated the effects of levodopa and STN-DBS on resting-state EEG and on the cortical-response profile to slow and fast RAS in a passive-listening paradigm focusing on beta-band oscillations, which are important for auditory–motor coupling. The beta-modulation profile to RAS in healthy participants was characterized by local peaks preceding and following auditory stimuli. In PD patients RAS failed to induce pre-stimulus beta increases. The absence of pre-stimulus beta-band modulation may contribute to impaired rhythm perception in PD. Moreover, post-stimulus beta-band responses were highly abnormal during fast RAS in PD patients. Treatment with levodopa and STN-DBS reinstated a post-stimulus beta-modulation profile similar to controls, while STN-DBS reduced beta-band power in the resting-state. The treatment-sensitivity of beta oscillations suggests that STN-DBS may specifically improve timekeeping functions of cortical beta oscillations during fast auditory pacing. PMID:26594626

  3. Load-Dependent Interference of Deep Brain Stimulation of the Subthalamic Nucleus with Switching from Automatic to Controlled Processing During Random Number Generation in Parkinson’s Disease

    PubMed Central

    Williams, Isobel Anne; Wilkinson, Leonora; Limousin, Patricia; Jahanshahi, Marjan

    2015-01-01

    Background: Deep brain stimulation of the subthalamic nucleus (STN DBS) ameliorates the motor symptoms of Parkinson’s disease (PD). However, some aspects of executive control are impaired with STN DBS. Objective: We tested the prediction that (i) STN DBS interferes with switching from automatic to controlled processing during fast-paced random number generation (RNG) (ii) STN DBS-induced cognitive control changes are load-dependent. Methods: Fifteen PD patients with bilateral STN DBS performed paced-RNG, under three levels of cognitive load synchronised with a pacing stimulus presented at 1, 0.5 and 0.33 Hz (faster rates require greater cognitive control), with DBS on or off. Measures of output randomness were calculated. Countscore 1 (CS1) indicates habitual counting in steps of one (CS1). Countscore 2 (CS2) indicates a more controlled strategy of counting in twos. Results: The fastest rate was associated with an increased CS1 score with STN DBS on compared to off. At the slowest rate, patients had higher CS2 scores with DBS off than on, such that the differences between CS1 and CS2 scores disappeared. Conclusions: We provide evidence for a load-dependent effect of STN DBS on paced RNG in PD. Patients could switch to more controlled RNG strategies during conditions of low cognitive load at slower rates only when the STN stimulators were off, but when STN stimulation was on, they engaged in more automatic habitual counting under increased cognitive load. These findings are consistent with the proposal that the STN implements a switch signal from the medial frontal cortex which enables a shift from automatic to controlled processing. PMID:25720447

  4. Cognition and Depression Following Deep Brain Stimulation of the Subthalamic Nucleus and Globus Pallidus Pars Internus in Parkinson's Disease: A Meta-Analysis.

    PubMed

    Combs, Hannah L; Folley, Bradley S; Berry, David T R; Segerstrom, Suzanne C; Han, Dong Y; Anderson-Mooney, Amelia J; Walls, Brittany D; van Horne, Craig

    2015-12-01

    Parkinson's disease (PD) is a common, degenerative disorder of the central nervous system. Individuals experience predominantly extrapyramidal symptoms including resting tremor, rigidity, bradykinesia, gait abnormalities, cognitive impairment, depression, and neurobehavioral concerns. Cognitive impairments associated with PD are diverse, including difficulty with attention, processing speed, executive functioning, memory recall, visuospatial functions, word-retrieval, and naming. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidus internus (GPi) is FDA approved and has been shown to be effective in reducing motor symptoms of PD. Studies have found that stimulating STN and GPi are equally effective at improving motor symptoms and dyskinesias; however, there has been discrepancy as to whether the cognitive, behavioral, and mood symptoms are affected differently between the two targets. The present study used random-effects meta-analytic models along with a novel p-curve analytic procedure to compare the potential cognitive and emotional impairments associated with STN-DBS in the current literature to those associated with GPi-DBS. Forty-one articles were reviewed with an aggregated sample size of 1622 patients. Following STN-DBS, small declines were found in psychomotor speed, memory, attention, executive functions, and overall cognition; and moderate declines were found in both semantic and phonemic fluency. However, GPi-DBS resulted in fewer neurocognitive declines than STN-DBS (small declines in attention and small-moderate declines in verbal fluency). With regards to its effect on depression symptomatology, both GPi-DBS and STN-DBS resulted in lower levels of depressive symptoms post-surgery. From a neurocognitive standpoint, both GPi-DBS and STN-DBS produce subtle cognitive declines but appears to be relatively well tolerated.

  5. Neuropsychological performance changes following subthalamic versus pallidal deep brain stimulation in Parkinson's disease: a systematic review and metaanalysis.

    PubMed

    Elgebaly, Ahmed; Elfil, Mohamed; Attia, Attia; Magdy, Mayar; Negida, Ahmed

    2017-02-27

    Studies comparing subthalamus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) for the management of Parkinson's disease in terms of neuropsychological performance are scarce and heterogeneous. Therefore, we performed a systematic review and metaanalysis to compare neuropsychological outcomes following STN DBS versus GPi DBS. A computer literature search of PubMed, the Web of Science, and Cochrane Central was conducted. Records were screened for eligible studies, and data were extracted and synthesized using Review Manager (v. 5.3 for Windows). Seven studies were included in the qualitative synthesis. Of them, four randomized controlled trials (n=345 patients) were pooled in the metaanalysis models. The standardized mean difference (SMD) of change in the Stroop color-naming test favored the GPi DBS group (SMD=-0.31, p=0.009). However, other neuropsychological outcomes did not favor either of the two groups (Stroop word-reading: SMD=-0.21, p=0.08; the Wechsler Adult Intelligence Scale (WAIS) digits forward: SMD=0.08, p=0.47; Trail Making Test Part A: SMD=-0.05, p=0.65; WAIS-R digit symbol: SMD=-0.16, p=0.29; Trail Making Test Part B: SMD=-0.14, p=0.23; Stroop color-word interference: SMD=-0.16, p=0.18; phonemic verbal fluency: bilateral DBS SMD=-0.04, p=0.73, and unilateral DBS SMD=-0.05, p=0.83; semantic verbal fluency: bilateral DBS SMD=-0.09, p=0.37, and unilateral DBS SMD=-0.29, p=0.22; Boston Naming Test: SMD=-0.11, p=0.33; Beck Depression Inventory: bilateral DBS SMD=0.15, p=0.31, and unilateral DBS SMD=0.36, p=0.11). There was no statistically significant difference in most of the neuropsychological outcomes. The present evidence does not favor any of the targets in terms of neuropsychological performance.

  6. Probabilistic versus deterministic tractography for delineation of the cortico-subthalamic hyperdirect pathway in patients with Parkinson disease selected for deep brain stimulation.

    PubMed

    Petersen, Mikkel V; Lund, Torben E; Sunde, Niels; Frandsen, Jesper; Rosendal, Frederikke; Juul, Niels; Østergaard, Karen

    2017-05-01

    OBJECTIVE Diffusion-weighted MRI (DWI) and tractography allows noninvasive mapping of the structural connections of the brain, and may provide important information for neurosurgical planning. The hyperdirect pathway, connecting the subthalamic nucleus (STN) with the motor cortex, is assumed to play a key role in mediating the effects of deep brain stimulation (DBS), which is an effective but poorly understood treatment for Parkinson disease. This study aimed to apply recent methodological advances in DWI acquisition and analysis to the delineation of the hyperdirect pathway in patients with Parkinson disease selected for surgery. METHODS High spatial and angular resolution DWI data were acquired preoperatively from 5 patients with Parkinson disease undergoing DBS. The authors compared the delineated hyperdirect pathways and associated STN target maps generated by 2 different tractography methods: a tensor-based deterministic method, typically available in clinical settings, and an advanced probabilistic method based on constrained spherical deconvolution. In addition, 10 high-resolution data sets with the same scanning parameters were acquired from a healthy control participant to assess the robustness of the tractography results. RESULTS Both tractography approaches identified connections between the ipsilateral motor cortex and the STN. However, the 2 methods provided substantially different target regions in the STN, with the target center of gravity differing by > 1.4 mm on average. The probabilistic method (based on constrained spherical deconvolution) plausibly reconstructed a continuous set of connections from the motor cortex, terminating in the dorsolateral region of the STN. In contrast, the tensor-based method reconstructed a comparatively sparser and more variable subset of connections. Furthermore, across the control scans, the probabilistic method identified considerably more consistent targeting regions within the STN compared with the deterministic

  7. Deep brain stimulation of pallidal versus subthalamic for patients with Parkinson’s disease: a meta-analysis of controlled clinical trials

    PubMed Central

    Xu, Fan; Ma, Wenbin; Huang, Yongmin; Qiu, Zhihai; Sun, Lei

    2016-01-01

    Background Parkinson’s disease (PD) is a common neurodegenerative disorder that affects many people every year. Deep brain stimulation (DBS) is an effective nonpharmacological method to treat PD motor symptoms. This meta-analysis was conducted to evaluate the efficacy of subthalamic nucleus (STN)-DBS versus globus pallidus internus (GPi)-DBS in treating advanced PD. Methods Controlled clinical trials that compared STN-DBS to GPi-DBS for short-term treatment of PD in adults were researched up to November 2015. The primary outcomes were the Unified Parkinson’s Disease Rating Scale Section (UPDRS) III score and the levodopa-equivalent dosage (LED) after DBS. The secondary outcomes were the UPDRS II score and the Beck Depression Inventory (BDI) score. Results Totally, 13 studies containing 1,148 PD patients were included in this meta-analysis to compare STN-DBS versus GPi-DBS. During the off-medication state, the pooled weighted mean difference (WMD) of UPDRS III and II scores were −2.18 (95% CI =−5.11 to 0.74) and −1.96 (95% CI =−3.84 to −0.08), respectively. During the on-medication state, the pooled WMD of UPDRS III and II scores were 0.15 (95% CI =−1.14 to 1.44) and 1.01 (95% CI =0.12 to 1.89), respectively. After DBS, the pooled WMD of LED and BDI were −254.48 (95% CI =−341.66) and 2.29 (95% CI =0.83 to 3.75), respectively. Conclusion These results indicate that during the off-medication state, the STN-DBS might be superior to GPi-DBS in improving the motor function and activities of daily living for PD patients; but during the on-medication state, the opposite result is observed. Meanwhile, the STN-DBS is superior at reducing the LED, whereas the GPi-DBS shows a significantly greater reduction in BDI score after DBS. PMID:27382286

  8. Greater improvement in LRRK2 G2019S patients undergoing Subthalamic Nucleus Deep Brain Stimulation compared to non-mutation carriers.

    PubMed

    Sayad, Massiva; Zouambia, Mohamed; Chaouch, Malika; Ferrat, Farida; Nebbal, Mustapha; Bendini, Mohamed; Lesage, Suzanne; Brice, Alexis; Brahim Errahmani, Mohamed; Asselah, Boualem

    2016-02-01

    Bilateral subthalamic nucleus deep brain stimulation (STN-DBS) of parkinson's disease (PD) patients has demonstrated to improve motor performance and to reduce dopa-induced dyskinesia. An association between the occurrence of dyskinesias and LRRK2 (leucine-rich repeat kinase 2) G2019S gene mutations has recently been suggested. The aim of this study is to discover the impact of the G2019S mutation (with high incidence in the authors' native Algeria) on the symptom response of PD in patients who underwent STN-DBS. We carried out a comparative statistical study for the clinical evaluation and neuropsychological assessment of 27 Algerian PD STN-DBS patients, both G2019S mutation carriers (MC) and non-carriers (NC). A multiple correspondence analysis (MCA) was then conducted to compare the results with those from groups of individuals with similar modalities. The MCA revealed that MC and NC PD patients showed two different patterns of clinical evaluations. The group of idiopathic patients showed some differences compared to the clinical evaluations, depending on gender. No association was found between the G2019S mutation and the Mini Mental State Examination scores (MMSE), and MC patients appeared more susceptible to dyskinesia than NC patients. In NC patients, we found two cases with Parkin mutations who had a different "honeymoon" period and different initial symptoms. The results showed considerable improvement of motor unified parkinson's disease rating scale III (UPDRS-III) in a situation of stimulation without medication in the MC patients with a percentage of improvement (51.1 %) over the required 30 % compared to the NC patients (25.5 %). The same result was observed for the Schwab and England's activities of daily living scale (S and E scale), which thus demonstrated a greater effectiveness of DBS for MC patients than for NC patients. However, the Hoehn and Yahr scale (H and Y Scale) showed the same significance in a situation of stimulation for MC and NC

  9. Implantation of electrodes for deep brain stimulation of the subthalamic nucleus in advanced Parkinson's disease with the aid of intraoperative microrecording under general anesthesia.

    PubMed

    Hertel, Frank; Züchner, Mark; Weimar, Inge; Gemmar, Peter; Noll, Bernhard; Bettag, Martin; Decker, Christian

    2006-11-01

    Deep brain stimulation (DBS) is widely accepted in the treatment of advanced Parkinson's disease (PD) and other movement disorders. The standard implantation procedure is performed under local anesthesia (LA). Certain groups of patients may not be eligible for surgery under LA because of clinical reasons, such as massive fear, reduced cooperativity, or coughing attacks. Microrecording (MER) has been shown to be helpful in DBS surgery. The purpose of this study was to evaluate the feasibility of MER for DBS surgery under general anesthesia (GA) and to compare the data of intraoperative MER as well as the clinical data with that of the current literature of patients undergoing operation under LA. The data of nine patients with advanced PD (mean Hoehn and Yahr status, 4.2) who were operated with subthalamic nucleus (STN) DBS under GA, owing to certain clinical circumstances ruling out DBS under LA, were retrospectively analyzed. All operations were performed under analgosedation with propofol or remifentanil and intraoperative MER. For MER, remifentanil was ceased completely and propofol was lowered as far as possible. The STN could be identified intraoperatively in all patients with MER. The typical bursting pattern was identified, whereas a widening of the baseline noise could not be as adequately detected as in patients under LA. The daily off phases of the patients were reduced from 50 to 17%, whereas the Unified Parkinson's Disease Rating Scale III score was reduced from 43 (preoperative, medication off) to 19 (stimulation on, medication off) and 12 (stimulation on, medication on). Two patients showed a transient neuropsychological deterioration after surgery, but both also had preexisting episodes of disorientation. One implantable pulse generator infection was noticed. No further significant clinical complications were observed. STN surgery for advanced PD with MER guidance is possible with good clinical results under GA. Intraoperative MER of the STN region

  10. Reversible improvement in severe freezing of gait from Parkinson's disease with unilateral interleaved subthalamic brain stimulation.

    PubMed

    Brosius, Stephanie N; Gonzalez, Christopher L; Shuresh, Joshita; Walker, Harrison C

    2015-12-01

    Freezing of gait causes considerable morbidity in patients with Parkinson's disease and is often refractory to conventional treatments. In this double-blind, randomized evaluation, unilateral interleaved deep brain stimulation in the subthalamic nucleus/substantia nigra pars reticulata region significantly improved freezing of gait in a patient with advanced Parkinson's disease.

  11. Deep brain stimulation modulates synchrony within spatially and spectrally distinct resting state networks in Parkinson's disease.

    PubMed

    Oswal, Ashwini; Beudel, Martijn; Zrinzo, Ludvic; Limousin, Patricia; Hariz, Marwan; Foltynie, Tom; Litvak, Vladimir; Brown, Peter

    2016-05-01

    Chronic dopamine depletion in Parkinson's disease leads to progressive motor and cognitive impairment, which is associated with the emergence of characteristic patterns of synchronous oscillatory activity within cortico-basal-ganglia circuits. Deep brain stimulation of the subthalamic nucleus is an effective treatment for Parkinson's disease, but its influence on synchronous activity in cortico-basal-ganglia loops remains to be fully characterized. Here, we demonstrate that deep brain stimulation selectively suppresses certain spatially and spectrally segregated resting state subthalamic nucleus-cortical networks. To this end we used a validated and novel approach for performing simultaneous recordings of the subthalamic nucleus and cortex using magnetoencephalography (during concurrent subthalamic nucleus deep brain stimulation). Our results highlight that clinically effective subthalamic nucleus deep brain stimulation suppresses synchrony locally within the subthalamic nucleus in the low beta oscillatory range and furthermore that the degree of this suppression correlates with clinical motor improvement. Moreover, deep brain stimulation relatively selectively suppressed synchronization of activity between the subthalamic nucleus and mesial premotor regions, including the supplementary motor areas. These mesial premotor regions were predominantly coupled to the subthalamic nucleus in the high beta frequency range, but the degree of deep brain stimulation-associated suppression in their coupling to the subthalamic nucleus was not found to correlate with motor improvement. Beta band coupling between the subthalamic nucleus and lateral motor areas was not influenced by deep brain stimulation. Motor cortical coupling with subthalamic nucleus predominantly involved driving of the subthalamic nucleus, with those drives in the higher beta frequency band having much shorter net delays to subthalamic nucleus than those in the lower beta band. These observations raise the

  12. Evaluation of the effects of deep brain stimulation of the subthalamic nucleus and levodopa treatment on Parkinsonian voice using perturbation, nonlinear dynamic, and perceptual analysis

    PubMed Central

    Zhou, Xiao Ping; Lee, Victoria S.; Wang, Emily Q.; Jiang, Jack J.

    2016-01-01

    Background/Aims To quantify aperiodic phonation, nonlinear dynamic methods of acoustic voice analysis, such as correlation dimension, have been shown to be useful. The purpose of this study is to evaluate the validity of nonlinear dynamic analysis as a voice analysis tool for the Parkinson’s disease (PD) treatment effects of deep brain stimulation (DBS) and levodopa. Methods In this study, the effects of DBS and levodopa treatment on patients with PD were measured using perturbation, nonlinear dynamic, and perceptual analysis. 19 PD patients that received bilateral (n=9), left, (n=7), or right (n=3) DBS performed sustained vowel phonations, which were recorded before- and after-medication with the stimulator-off and -on. Recordings were also taken of 10 PD patients that did not receive DBS surgery before- and after-medication to provide a baseline. Results A mixed two-way ANOVA (surgery, medication) generated significant positive treatment effects of DBS only in mean log-transformed D2, which was supported by mean log-transformed shimmer, vF0, and vAm. Conclusion These findings may indicate the validity of nonlinear dynamic analysis as a complement to perceptual analysis in clinical PD voice studies. PMID:19590218

  13. Identification of VPS35 p.D620N mutation-related Parkinson's disease in a Taiwanese family with successful bilateral subthalamic nucleus deep brain stimulation: a case report and literature review.

    PubMed

    Chen, Ying-Fa; Chang, Yung-Yee; Lan, Min-Yu; Chen, Pei-Lung; Lin, Chin-Hsien

    2017-10-06

    Vacuolar protein sorting 35 (VPS35) was recently reported to be a genetic cause for late-onset autosomal dominant Parkinson's disease (PD). However, VPS35 mutations are rarely reported in Asian populations. Herein, we report the first Taiwanese family with the pathogenic VPS35 p.D620N mutation, including one patient treated successfully with subthalamic nucleus deep brain stimulation (STN-DBS). A 61-year-old woman presented with progressive left hand resting tremor at the age of 42. Neurological examinations revealed mask face and akinetic-rigidity over left extremities. She showed a good response to levodopa treatment, and her unified Parkinson's disease rating scale (UPDRS) motor scores improved from 42 to 15 under the levodopa equivalent dose of 1435 mg/day. She developed peak-dose dyskinesia and motor fluctuation seven years after the onset of symptoms, and received bilateral STN-DBS at the age of 55. Stimulation led to a marked improvement in her motor symptoms with a 37% improvement in the UPDRS motor score during the OFF period five years after surgery. The patient's mother and three siblings were also diagnosed with PD in their forties, following an autosomal-dominant inheritance pattern. We performed genetic analysis of the proband using a targeted next generation sequencing (NGS) panel covering 17 known PD-causative genes. We identified a pathogenic missense mutation in VPS35 gene, c.1858G > A (p.D620N), in this patient. This is the first report of the VPS35 p.D620N mutation in a Taiwanese family. Additionally, our report contributes to the current understanding of genetically defined PD patients treated successfully with STN-DBS.

  14. Targeting the subthalamic nucleus for deep brain stimulation: technical approach and fusion of pre- and postoperative MR images to define accuracy of lead placement.

    PubMed

    Hamid, N A; Mitchell, R D; Mocroft, P; Westby, G W M; Milner, J; Pall, H

    2005-03-01

    To define the role of magnetic resonance imaging (MRI) and intraoperative electrophysiological recording in targeting the subthalamic nucleus (STN) in Parkinson's disease and to determine accuracy of electrode placement. We implanted 54 electrodes into the STN in 27 patients. Target planning was done by coordinate guidelines and visualising the STN on MRI and defined in relation to the mid-point of the AC-PC line. Intraoperative microelectrode recording was used. We adjusted electrode positions for placement in the centre of the STN electrical activity and verified this on postoperative MRI in 16 cases, which were fused to the preoperative images to measure actual error in electrode placement in the three axes. Based on coordinate calculation and MRI localisation, the mean of the target was 11.5 mm lateral, 2.5 mm posterior and 4.1 mm inferior to the mid-point of the AC-PC line. Fifty good electrophysiological recordings of the STN (average length 4.65 mm) were achieved and target point adjusted in 90% of lead placements. The mean of the final target after electrophysiological correction was 11.7 mm lateral, 2.1 mm posterior, and 3.8 mm inferior to the mid-point. The distance from the centre of the electrode artefact to the final target used after electrophysiological recording on the fused images was 0.48 mm, 0.69 mm, and 2.9 mm in the x, y, and z axes, respectively. No postoperative MRI related complication was observed. Both direct visualisation of the STN on MRI and intraoperative electrophysiological recording are important in defining the best target. Individual variations exist in the location of the STN target. Fewer tracks were required to define STN activity on the side operated first. Our current stereotactic method of electrode placement is relatively accurate.

  15. Deep brain stimulation modulates synchrony within spatially and spectrally distinct resting state networks in Parkinson’s disease

    PubMed Central

    Oswal, Ashwini; Beudel, Martijn; Zrinzo, Ludvic; Limousin, Patricia; Hariz, Marwan; Foltynie, Tom; Litvak, Vladimir

    2016-01-01

    Chronic dopamine depletion in Parkinson’s disease leads to progressive motor and cognitive impairment, which is associated with the emergence of characteristic patterns of synchronous oscillatory activity within cortico-basal-ganglia circuits. Deep brain stimulation of the subthalamic nucleus is an effective treatment for Parkinson’s disease, but its influence on synchronous activity in cortico-basal-ganglia loops remains to be fully characterized. Here, we demonstrate that deep brain stimulation selectively suppresses certain spatially and spectrally segregated resting state subthalamic nucleus–cortical networks. To this end we used a validated and novel approach for performing simultaneous recordings of the subthalamic nucleus and cortex using magnetoencephalography (during concurrent subthalamic nucleus deep brain stimulation). Our results highlight that clinically effective subthalamic nucleus deep brain stimulation suppresses synchrony locally within the subthalamic nucleus in the low beta oscillatory range and furthermore that the degree of this suppression correlates with clinical motor improvement. Moreover, deep brain stimulation relatively selectively suppressed synchronization of activity between the subthalamic nucleus and mesial premotor regions, including the supplementary motor areas. These mesial premotor regions were predominantly coupled to the subthalamic nucleus in the high beta frequency range, but the degree of deep brain stimulation-associated suppression in their coupling to the subthalamic nucleus was not found to correlate with motor improvement. Beta band coupling between the subthalamic nucleus and lateral motor areas was not influenced by deep brain stimulation. Motor cortical coupling with subthalamic nucleus predominantly involved driving of the subthalamic nucleus, with those drives in the higher beta frequency band having much shorter net delays to subthalamic nucleus than those in the lower beta band. These observations raise

  16. Three-dimensional SPACE fluid-attenuated inversion recovery at 3 T to improve subthalamic nucleus lead placement for deep brain stimulation in Parkinson's disease: from preclinical to clinical studies.

    PubMed

    Senova, Suhan; Hosomi, Koichi; Gurruchaga, Jean-Marc; Gouello, Gaëtane; Ouerchefani, Naoufel; Beaugendre, Yara; Lepetit, Hélène; Lefaucheur, Jean-Pascal; Badin, Romina Aron; Dauguet, Julien; Jan, Caroline; Hantraye, Philippe; Brugières, Pierre; Palfi, Stéphane

    2016-08-01

    OBJECTIVE Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established therapy for motor symptoms in patients with pharmacoresistant Parkinson's disease (PD). However, the procedure, which requires multimodal perioperative exploration such as imaging, electrophysiology, or clinical examination during macrostimulation to secure lead positioning, remains challenging because the STN cannot be reliably visualized using the gold standard, T2-weighted imaging (T2WI) at 1.5 T. Thus, there is a need to improve imaging tools to better visualize the STN, optimize DBS lead implantation, and enlarge DBS diffusion. METHODS Gradient-echo sequences such as those used in T2WI suffer from higher distortions at higher magnetic fields than spin-echo sequences. First, a spin-echo 3D SPACE (sampling perfection with application-optimized contrasts using different flip angle evolutions) FLAIR sequence at 3 T was designed, validated histologically in 2 nonhuman primates, and applied to 10 patients with PD; their data were clinically compared in a double-blind manner with those of a control group of 10 other patients with PD in whom STN targeting was performed using T2WI. RESULTS Overlap between the nonhuman primate STNs segmented on 3D-histological and on 3D-SPACE-FLAIR volumes was high for the 3 most anterior quarters (mean [± SD] Dice scores 0.73 ± 0.11, 0.74 ± 0.06, and 0.60 ± 0.09). STN limits determined by the 3D-SPACE-FLAIR sequence were more consistent with electrophysiological edges than those determined by T2WI (0.9 vs 1.4 mm, respectively). The imaging contrast of the STN on the 3D-SPACE-FLAIR sequence was 4 times higher (p < 0.05). Improvement in the Unified Parkinson's Disease Rating Scale Part III score (off medication, on stimulation) 12 months after the operation was higher for patients who underwent 3D-SPACE-FLAIR-guided implantation than for those in whom T2WI was used (62.2% vs 43.6%, respectively; p < 0.05). The total electrical energy

  17. Subthalamic deep brain stimulation in Parkinson׳s disease has no significant effect on perceptual timing in the hundreds of milliseconds range

    PubMed Central

    Cope, Thomas E.; Grube, Manon; Mandal, Arnab; Cooper, Freya E.; Brechany, Una; Burn, David J.; Griffiths, Timothy D.

    2014-01-01

    Bilateral, high-frequency stimulation of the basal ganglia (STN-DBS) is in widespread use for the treatment of the motor symptoms of Parkinson׳s disease (PD). We present here the first psychophysical investigation of the effect of STN-DBS upon perceptual timing in the hundreds of milliseconds range, with both duration-based (absolute) and beat-based (relative) tasks; 13 patients with PD were assessed with their STN-DBS ‘on’, ‘off’, and then ‘on’ again. Paired parametric analyses revealed no statistically significant differences for any task according to DBS status. We demonstrate, from the examination of confidence intervals, that any functionally relevant effect of STN-DBS on relative perceptual timing is statistically unlikely. For absolute, duration-based timing, we demonstrate that the activation of STN-DBS may either worsen performance or have no effect, but that it is unlikely to lead to significant improvement. Although these results are negative they have important implications for our understanding of perceptual timing and its relationship to motor functions within the timing network of the brain. They imply that the mechanisms involved in the perceptual processing of temporal information are likely to be functionally independent from those that underpin movement. Further, they suggest that the connections between STN and the subtantia nigra and globus pallidus are unlikely to be critical to beat-based perceptual timing. PMID:24613477

  18. Deep brain stimulation modulates effects of motivation in Parkinson's disease.

    PubMed

    Sauleau, Paul; Eusebio, Alexandre; Vandenberghe, Wim; Nuttin, Bart; Brown, Peter

    2009-04-22

    It is unclear how motivation leads to improved motor performance. Here we test the hypothesis that motivation interacts with behavioural performance in the basal ganglia. We recorded trial-to-trial performance in a bimanual motor task in 10 patients with Parkinson's disease with electrodes chronically implanted in the subthalamic nucleus for deep brain stimulation. Motivation-associated improvements in trial-to-trial performance were contrasted with and without stimulation at high frequency. Motivation and stimulation improved trial-to-trial performance, but the effect of motivation was halved during stimulation. We conclude that the subthalamic area is mechanistically important in those processes linking motivation to improvement in motor performance. This finding may be relevant to some of the cognitive and emotional changes associated with bilateral subthalamic stimulation.

  19. Deep brain light stimulation effects on glutamate and dopamine concentration.

    PubMed

    Kuo, Jinn-Rung; Lin, Shih-Shian; Liu, Janelle; Chen, Shih-How; Chio, Chung-Chin; Wang, Jhi-Joung; Liu, Jia-Ming

    2015-01-01

    Compared to deep brain electrical stimulation, which has been applied to treating pathological brain diseases, little work has been done on the effect of deep brain light stimulation. A fiber-coupled laser stimulator at 840 nm wavelength and 130 Hz pulse repetition rate is developed in this work for deep brain light stimulation in a rat model. Concentration changes in glutamate and dopamine in the striatum are observed using a microdialysis probe when the subthalamic nucleus (STN) is stimulated at various optical power levels. Experimental results show that light stimulation causes the concentration of glutamate to decrease while that of dopamine is increased. This suggests that deep brain light stimulation of the STN is a promising therapeutic strategy for dopamine-related diseases such as Parkinson's disease. The stimulator developed for this work is useful for deep brain light stimulation in biomedical research.

  20. Chaotic Desynchronization as the Therapeutic Mechanism of Deep Brain Stimulation

    PubMed Central

    Wilson, Charles J.; Beverlin, Bryce; Netoff, Theoden

    2011-01-01

    High frequency deep-brain stimulation of the subthalamic nucleus (deep brain stimulation, DBS) relieves many of the symptoms of Parkinson's disease in humans and animal models. Although the treatment has seen widespread use, its therapeutic mechanism remains paradoxical. The subthalamic nucleus is excitatory, so its stimulation at rates higher than its normal firing rate should worsen the disease by increasing subthalamic excitation of the globus pallidus. The therapeutic effectiveness of DBS is also frequency and intensity sensitive, and the stimulation must be periodic; aperiodic stimulation at the same mean rate is ineffective. These requirements are not adequately explained by existing models, whether based on firing rate changes or on reduced bursting. Here we report modeling studies suggesting that high frequency periodic excitation of the subthalamic nucleus may act by desynchronizing the firing of neurons in the globus pallidus, rather than by changing the firing rate or pattern of individual cells. Globus pallidus neurons are normally desynchronized, but their activity becomes correlated in Parkinson's disease. Periodic stimulation may induce chaotic desynchronization by interacting with the intrinsic oscillatory mechanism of globus pallidus neurons. Our modeling results suggest a mechanism of action of DBS and a pathophysiology of Parkinsonism in which synchrony, rather than firing rate, is the critical pathological feature. PMID:21734868

  1. Deep Brain Stimulation for Parkinson Disease

    PubMed Central

    Bronstein, Jeff M.; Tagliati, Michele; Alterman, Ron L.; Lozano, Andres M.; Volkmann, Jens; Stefani, Alessandro; Horak, Fay B.; Okun, Michael S.; Foote, Kelly D.; Krack, Paul; Pahwa, Rajesh; Henderson, Jaimie M.; Hariz, Marwan I.; Bakay, Roy A.; Rezai, Ali; Marks, William J.; Moro, Elena; Vitek, Jerrold L.; Weaver, Frances M.; Gross, Robert E.; DeLong, Mahlon R.

    2015-01-01

    Objective To provide recommendations to patients, physicians, and other health care providers on several issues involving deep brain stimulation (DBS) for Parkinson disease (PD). Data Sources and Study Selection An international consortium of experts organized, reviewed the literature, and attended the workshop. Topics were introduced at the workshop, followed by group discussion. Data Extraction and Synthesis A draft of a consensus statement was presented and further edited after plenary debate. The final statements were agreed on by all members. Conclusions (1) Patients with PD without significant active cognitive or psychiatric problems who have medically intractable motor fluctuations, intractable tremor, or intolerance of medication adverse effects are good candidates for DBS. (2) Deep brain stimulation surgery is best performed by an experienced neurosurgeon with expertise in stereotactic neurosurgery who is working as part of a interprofessional team. (3) Surgical complication rates are extremely variable, with infection being the most commonly reported complication of DBS. (4) Deep brain stimulation programming is best accomplished by a highly trained clinician and can take 3 to 6 months to obtain optimal results. (5) Deep brain stimulation improves levodopa-responsive symptoms, dyskinesia, and tremor; benefits seem to be long-lasting in many motor domains. (6) Subthalamic nuclei DBS may be complicated by increased depression, apathy, impulsivity, worsened verbal fluency, and executive dysfunction in a subset of patients. (7) Both globus pallidus pars interna and subthalamic nuclei DBS have been shown to be effective in addressing the motor symptoms of PD. (8) Ablative therapy is still an effective alternative and should be considered in a select group of appropriate patients. PMID:20937936

  2. Resting state functional MRI in Parkinson's disease: the impact of deep brain stimulation on 'effective' connectivity.

    PubMed

    Kahan, Joshua; Urner, Maren; Moran, Rosalyn; Flandin, Guillaume; Marreiros, Andre; Mancini, Laura; White, Mark; Thornton, John; Yousry, Tarek; Zrinzo, Ludvic; Hariz, Marwan; Limousin, Patricia; Friston, Karl; Foltynie, Tom

    2014-04-01

    Depleted of dopamine, the dynamics of the parkinsonian brain impact on both 'action' and 'resting' motor behaviour. Deep brain stimulation has become an established means of managing these symptoms, although its mechanisms of action remain unclear. Non-invasive characterizations of induced brain responses, and the effective connectivity underlying them, generally appeals to dynamic causal modelling of neuroimaging data. When the brain is at rest, however, this sort of characterization has been limited to correlations (functional connectivity). In this work, we model the 'effective' connectivity underlying low frequency blood oxygen level-dependent fluctuations in the resting Parkinsonian motor network-disclosing the distributed effects of deep brain stimulation on cortico-subcortical connections. Specifically, we show that subthalamic nucleus deep brain stimulation modulates all the major components of the motor cortico-striato-thalamo-cortical loop, including the cortico-striatal, thalamo-cortical, direct and indirect basal ganglia pathways, and the hyperdirect subthalamic nucleus projections. The strength of effective subthalamic nucleus afferents and efferents were reduced by stimulation, whereas cortico-striatal, thalamo-cortical and direct pathways were strengthened. Remarkably, regression analysis revealed that the hyperdirect, direct, and basal ganglia afferents to the subthalamic nucleus predicted clinical status and therapeutic response to deep brain stimulation; however, suppression of the sensitivity of the subthalamic nucleus to its hyperdirect afferents by deep brain stimulation may subvert the clinical efficacy of deep brain stimulation. Our findings highlight the distributed effects of stimulation on the resting motor network and provide a framework for analysing effective connectivity in resting state functional MRI with strong a priori hypotheses.

  3. Reversing cognitive-motor impairments in Parkinson's disease patients using a computational modelling approach to deep brain stimulation programming.

    PubMed

    Frankemolle, Anneke M M; Wu, Jennifer; Noecker, Angela M; Voelcker-Rehage, Claudia; Ho, Jason C; Vitek, Jerrold L; McIntyre, Cameron C; Alberts, Jay L

    2010-03-01

    Deep brain stimulation in the subthalamic nucleus is an effective and safe surgical procedure that has been shown to reduce the motor dysfunction of patients with advanced Parkinson's disease. Bilateral subthalamic nucleus deep brain stimulation, however, has been associated with declines in cognitive and cognitive-motor functioning. It has been hypothesized that spread of current to nonmotor areas of the subthalamic nucleus may be responsible for declines in cognitive and cognitive-motor functioning. The aim of this study was to assess the cognitive-motor performance in advanced Parkinson's disease patients with subthalamic nucleus deep brain stimulation parameters determined clinically (Clinical) to settings derived from a patient-specific computational model (Model). Data were collected from 10 patients with advanced Parkinson's disease bilaterally implanted with subthalamic nucleus deep brain stimulation systems. These patients were assessed off medication and under three deep brain stimulation conditions: Off, Clinical or Model based stimulation. Clinical stimulation parameters had been determined based on clinical evaluations and were stable for at least 6 months prior to study participation. Model-based parameters were selected to minimize the spread of current to nonmotor portions of the subthalamic nucleus using Cicerone Deep Brain Stimulation software. For each stimulation condition, participants performed a working memory (n-back task) and motor task (force tracking) under single- and dual-task settings. During the dual-task, participants performed the n-back and force-tracking tasks simultaneously. Clinical and Model parameters were equally effective in improving the Unified Parkinson's disease Rating Scale III scores relative to Off deep brain stimulation scores. Single-task working memory declines, in the 2-back condition, were significantly less under Model compared with Clinical deep brain stimulation settings. Under dual-task conditions, force

  4. Pathological gambling in Parkinson's disease: subthalamic oscillations during economics decisions.

    PubMed

    Rosa, Manuela; Fumagalli, Manuela; Giannicola, Gaia; Marceglia, Sara; Lucchiari, Claudio; Servello, Domenico; Franzini, Angelo; Pacchetti, Claudio; Romito, Luigi; Albanese, Alberto; Porta, Mauro; Pravettoni, Gabriella; Priori, Alberto

    2013-10-01

    Pathological gambling develops in up to 8% of patients with Parkinson's disease. Although the pathophysiology of gambling remains unclear, several findings argue for a dysfunction in the basal ganglia circuits. To clarify the role of the subthalamic nucleus in pathological gambling, we studied its activity during economics decisions. We analyzed local field potentials recorded from deep brain stimulation electrodes in the subthalamic nucleus while parkinsonian patients with (n = 8) and without (n = 9) pathological gambling engaged in an economics decision-making task comprising conflictual trials (involving possible risk-taking) and non conflictual trials. In all parkinsonian patients, subthalamic low frequencies (2-12 Hz) increased during economics decisions. Whereas, in patients without gambling, low-frequency oscillations exhibited a similar pattern during conflictual and non conflictual stimuli, in those with gambling, low-frequency activity increased significantly more during conflictual than during non conflictual stimuli. The specific low-frequency oscillatory pattern recorded in patients with Parkinson's disease who gamble could reflect a subthalamic dysfunction that makes their decisional threshold highly sensitive to risky options. When parkinsonian patients process stimuli related to an economics task, low-frequency subthalamic activity increases. This task-related change suggests that the cognitive-affective system that drives economics decisional processes includes the subthalamic nucleus. The specific subthalamic neuronal activity during conflictual decisions in patients with pathological gambling supports the idea that the subthalamic nucleus is involved in behavioral strategies and in the pathophysiology of gambling. Copyright © 2013 Movement Disorder Society.

  5. Posterior occipitocervical instrumented fusion for dropped head syndrome after deep brain stimulation.

    PubMed

    Pereira, E A C; Wilson-MacDonald, J; Green, A L; Aziz, T Z; Cadoux-Hudson, T A D

    2010-04-01

    We describe dropped head syndrome in a patient with Parkinson's disease receiving subthalamic nucleus deep brain stimulation (DBS). Posterior occipitocervical instrumented fusion after transarticular screw fixation of an odontoid fracture is shown and its rationale explained. Pedunculopontine nucleus DBS as treatment for fall-predominant Parkinson's disease, and globus pallidus interna DBS for dystonia-predominant Parkinson's disease, are discussed.

  6. Movement disorders induced by deep brain stimulation.

    PubMed

    Baizabal-Carvallo, José Fidel; Jankovic, Joseph

    2016-04-01

    Deep brain stimulation represents a major advance in the treatment of several types of movement disorders. However, during stimulation new movement disorders may emerge, thus limiting the positive effects of this therapy. These movement disorders may be induced by: 1) stimulation of the targeted nucleus, 2) stimulation of surrounding tracts and nuclei, and 3) as a result of dose adjustment of accompanying medications, such as reduction of dopaminergic drugs in patients with Parkinson's disease. Various dyskinesias, blepharospasm, and apraxia of eyelid opening have been described mainly with subthalamic nucleus stimulation, whereas hypokinesia and freezing of gait have been observed with stimulation of the globus pallidus internus. Other deep brain stimulation-related movement disorders include dyskinesias associated with stimulation of the globus pallidus externus and ataxic gait as a side effect of chronic bilateral stimulation of the ventral intermediate nucleus of thalamus. These movement disorders are generally reversible and usually resolved once the stimulation is reduced or turned off. This, however, typically leads to loss of benefit of the underlying movement disorder which can be re-gained by using different contacts, changing targets or stimulation parameters, and adjusting pharmacological therapy. New and innovative emerging technologies and stimulation techniques may help to prevent or overcome the various deep brain stimulation-induced movement disorders. In this review we aim to describe the clinical features, frequency, pathophysiology, and strategies for treatment of these iatrogenic movement disorders.

  7. The subthalamic nucleus influences visuospatial attention in humans.

    PubMed

    Schmalbach, Barbara; Günther, Veronika; Raethjen, Jan; Wailke, Stefanie; Falk, Daniela; Deuschl, Günther; Witt, Karsten

    2014-03-01

    Spatial attention is a lateralized feature of the human brain. Whereas the role of cortical areas of the nondominant hemisphere on spatial attention has been investigated in detail, the impact of the BG, and more precisely the subthalamic nucleus, on signs and symptoms of spatial attention is not well understood. Here we used unilateral deep brain stimulation of the subthalamic nucleus to reversibly, specifically, and intraindividually modify the neuronal BG outflow and its consequences on signs and symptoms of visuospatial attention in patients suffering from Parkinson disease. We tested 13 patients with Parkinson disease and chronic deep brain stimulation in three stimulation settings: unilateral right and left deep brain stimulation of the subthalamic nucleus as well as bilateral deep brain stimulation of the subthalamic nucleus. In all three stimulation settings, the patients viewed a set of pictures while an eye-tracker system recorded eye movements. During the exploration of the visual stimuli, we analyzed the time spent in each visual hemispace, as well as the number, duration, amplitude, peak velocity, acceleration peak, and speed of saccades. In the unilateral left-sided stimulation setting, patients show a shorter ipsilateral exploration time of the extrapersonal space, whereas number, duration, and speed of saccades did not differ between the different stimulation settings. These results demonstrated reduced visuospatial attention toward the side contralateral to the right subthalamic nucleus that was not being stimulated in a unilateral left-sided stimulation. Turning on the right stimulator, the reduced visuospatial attention vanished. These results support the involvement of the subthalamic nucleus in modulating spatial attention. Therefore, the subthalamic nucleus is part of the subcortical network that subserves spatial attention.

  8. In vivo Exploration of the Connectivity between the Subthalamic Nucleus and the Globus Pallidus in the Human Brain Using Multi-Fiber Tractography

    PubMed Central

    Pujol, Sonia; Cabeen, Ryan; Sébille, Sophie B.; Yelnik, Jérôme; François, Chantal; Fernandez Vidal, Sara; Karachi, Carine; Zhao, Yulong; Cosgrove, G. Rees; Jannin, Pierre; Kikinis, Ron; Bardinet, Eric

    2017-01-01

    The basal ganglia is part of a complex system of neuronal circuits that play a key role in the integration and execution of motor, cognitive and emotional function in the human brain. Parkinson’s disease is a progressive neurological disorder of the motor circuit characterized by tremor, rigidity, and slowness of movement. Deep brain stimulation (DBS) of the subthalamic nucleus and the globus pallidus pars interna provides an efficient treatment to reduce symptoms and levodopa-induced side effects in Parkinson’s disease patients. While the underlying mechanism of action of DBS is still unknown, the potential modulation of white matter tracts connecting the surgical targets has become an active area of research. With the introduction of advanced diffusion MRI acquisition sequences and sophisticated post-processing techniques, the architecture of the human brain white matter can be explored in vivo. The goal of this study is to investigate the white matter connectivity between the subthalamic nucleus and the globus pallidus. Two multi-fiber tractography methods were used to reconstruct pallido-subthalamic, subthalamo-pallidal and pyramidal fibers in five healthy subjects datasets of the Human Connectome Project. The anatomical accuracy of the tracts was assessed by four judges with expertise in neuroanatomy, functional neurosurgery, and diffusion MRI. The variability among subjects was evaluated based on the fractional anisotropy and mean diffusivity of the tracts. Both multi-fiber approaches enabled the detection of complex fiber architecture in the basal ganglia. The qualitative evaluation by experts showed that the identified tracts were in agreement with the expected anatomy. Tract-derived measurements demonstrated relatively low variability among subjects. False-negative tracts demonstrated the current limitations of both methods for clinical decision-making. Multi-fiber tractography methods combined with state-of-the-art diffusion MRI data have the

  9. Deep brain stimulation for movement disorders.

    PubMed

    Larson, Paul S

    2014-07-01

    Deep brain stimulation (DBS) is an implanted electrical device that modulates specific targets in the brain resulting in symptomatic improvement in a particular neurologic disease, most commonly a movement disorder. It is preferred over previously used lesioning procedures due to its reversibility, adjustability, and ability to be used bilaterally with a good safety profile. Risks of DBS include intracranial bleeding, infection, malposition, and hardware issues, such migration, disconnection, or malfunction, but the risk of each of these complications is low--generally ≤ 5% at experienced, large-volume centers. It has been used widely in essential tremor, Parkinson's disease, and dystonia when medical treatment becomes ineffective, intolerable owing to side effects, or causes motor complications. Brain targets implanted include the thalamus (most commonly for essential tremor), subthalamic nucleus (most commonly for Parkinson's disease), and globus pallidus (Parkinson's disease and dystonia), although new targets are currently being explored. Future developments include brain electrodes that can steer current directionally and systems capable of "closed loop" stimulation, with systems that can record and interpret regional brain activity and modify stimulation parameters in a clinically meaningful way. New, image-guided implantation techniques may have advantages over traditional DBS surgery.

  10. Resting state functional MRI in Parkinson’s disease: the impact of deep brain stimulation on ‘effective’ connectivity

    PubMed Central

    Kahan, Joshua; Urner, Maren; Moran, Rosalyn; Flandin, Guillaume; Marreiros, Andre; Mancini, Laura; White, Mark; Thornton, John; Yousry, Tarek; Zrinzo, Ludvic; Hariz, Marwan; Limousin, Patricia; Friston, Karl

    2014-01-01

    Depleted of dopamine, the dynamics of the parkinsonian brain impact on both ‘action’ and ‘resting’ motor behaviour. Deep brain stimulation has become an established means of managing these symptoms, although its mechanisms of action remain unclear. Non-invasive characterizations of induced brain responses, and the effective connectivity underlying them, generally appeals to dynamic causal modelling of neuroimaging data. When the brain is at rest, however, this sort of characterization has been limited to correlations (functional connectivity). In this work, we model the ‘effective’ connectivity underlying low frequency blood oxygen level-dependent fluctuations in the resting Parkinsonian motor network—disclosing the distributed effects of deep brain stimulation on cortico-subcortical connections. Specifically, we show that subthalamic nucleus deep brain stimulation modulates all the major components of the motor cortico-striato-thalamo-cortical loop, including the cortico-striatal, thalamo-cortical, direct and indirect basal ganglia pathways, and the hyperdirect subthalamic nucleus projections. The strength of effective subthalamic nucleus afferents and efferents were reduced by stimulation, whereas cortico-striatal, thalamo-cortical and direct pathways were strengthened. Remarkably, regression analysis revealed that the hyperdirect, direct, and basal ganglia afferents to the subthalamic nucleus predicted clinical status and therapeutic response to deep brain stimulation; however, suppression of the sensitivity of the subthalamic nucleus to its hyperdirect afferents by deep brain stimulation may subvert the clinical efficacy of deep brain stimulation. Our findings highlight the distributed effects of stimulation on the resting motor network and provide a framework for analysing effective connectivity in resting state functional MRI with strong a priori hypotheses. PMID:24566670

  11. MR Anatomy of Deep Brain Nuclei with Special Reference to Specific Diseases and Deep Brain Stimulation Localization

    PubMed Central

    Telford, Ryan; Vattoth, Surjith

    2014-01-01

    Summary Diseases affecting the basal ganglia and deep brain structures vary widely in etiology and include metabolic, infectious, ischemic, and neurodegenerative conditions. Some neurologic diseases, such as Wernicke encephalopathy or pseudohypoparathyroidism, require specific treatments, which if unrecognized could lead to further complications. Other pathologies, such as hypertrophic olivary degeneration, if not properly diagnosed may be mistaken for a primary medullary neoplasm and create unnecessary concern. The deep brain structures are complex and can be difficult to distinguish on routine imaging. It is imperative that radiologists first understand the intrinsic anatomic relationships between the different basal ganglia nuclei and deep brain structures with magnetic resonance (MR) imaging. It is important to understand the "normal" MR signal characteristics, locations, and appearances of these structures. This is essential to recognizing diseases affecting the basal ganglia and deep brain structures, especially since most of these diseases result in symmetrical, and therefore less noticeable, abnormalities. It is also crucial that neurosurgeons correctly identify the deep brain nuclei presurgically for positioning deep brain stimulator leads, the most important being the subthalamic nucleus for Parkinson syndromes and the thalamic ventral intermediate nucleus for essential tremor. Radiologists will be able to better assist clinicians in diagnosis and treatment once they are able to accurately localize specific deep brain structures. PMID:24571832

  12. Cortico-muscular coherence increases with tremor improvement after deep brain stimulation in Parkinson's disease.

    PubMed

    Park, Hame; Kim, June Sic; Paek, Sun Ha; Jeon, Beom Seok; Lee, Jee Young; Chung, Chun Kee

    2009-10-28

    Deep brain stimulation on the subthalamic nucleus has been used to relieve Parkinsonian motor symptoms. However, the underlying physiological mechanism has not been fully understood. Beta-band cortico-muscular coherence increases when healthy humans perform isometric contraction. We hypothesized that this might be a measure of symptomatic improvement in motor performance after subthalamic nucleus deep brain stimulation. Here, we measured the beta-band cortico-muscular coherence with magnetoencephalography from three Parkinson's disease patients. We then compared the coherence values for stimulator on-state and off-state. We found that when the stimulator is on, the beta cortico-muscular coherence elevates significantly for the tremorous hand compared with that when the stimulator is off. This suggests that deep brain stimulation resulted in better cortico-muscular coordination.

  13. Recording of the Neural Activity Induced by the Electrical Subthalamic Stimulation Using Ca2+ Imaging

    NASA Astrophysics Data System (ADS)

    Tamura, Atsushi; Yagi, Tetsuya; Osanai, Makoto

    The basal ganglia (BG) have important roles in some kind of motor control and learning. Parkinson's disease is one of the motor impairment disease. Recently, to recover a motor severity in patients of Parkinsonism, the stimulus electrode is implanted to the subthalamic nucleus, which is a part of the basal ganglia, and the deep brain stimulation (DBS) is often conducted. However, the effects of the DBS on the subthalamic neurons have not been elucidated. Thus, to analyze the effects of the electrical stimulation on the subthalamic neurons, we conducted the calcium imaging at the mouse subthalamic nucleus. When the single stimulus was applied to the subthalamic nucleus, the intracellular calcium ([Ca2+]i) transients were observed. In the case of application of the single electrical stimulation, the [Ca2+]i arose near the stimulus position. When 100 Hz 10-100 times tetanic stimulations were applied, the responded area and the amplitudes of [Ca2+]i transients were increased. The [Ca2+]i transients were disappeared almost completely on the action potential blockade, but blockade of the excitatory and the inhibitory synaptic transmission had little effects on the responded area and the amplitudes of the [Ca2+]i transients. These results suggested that the electrical stimulation to the subthalamic neurons led to activate the subthalamic neurons directly but not via synaptic transmissions. Thus, DBS may change the activity of the subthalamic neurons, hence, may alter the input-output relationship of the subthalamic neurons

  14. Deep Brain Stimulation

    PubMed Central

    Chen, X.L.; Xiong, Y.Y.; Xu, G.L.; Liu, X.F.

    2013-01-01

    Deep brain stimulation (DBS) has provided remarkable therapeutic benefits for people with a variety of neurological disorders. Despite the uncertainty of the precise mechanisms underlying its efficacy, DBS is clinically effective in improving motor function of essential tremor, Parkinson's disease and primary dystonia and in relieving obsessive-compulsive disorder. Recently, this surgical technique has continued to expand to other numerous neurological diseases with encouraging results. This review highlighted the current and potential future clinical applications of DBS. PMID:25187779

  15. The modulatory effect of adaptive deep brain stimulation on beta bursts in Parkinson’s disease

    PubMed Central

    Tinkhauser, Gerd; Pogosyan, Alek; Little, Simon; Beudel, Martijn; Herz, Damian M.; Tan, Huiling

    2017-01-01

    Abstract Adaptive deep brain stimulation uses feedback about the state of neural circuits to control stimulation rather than delivering fixed stimulation all the time, as currently performed. In patients with Parkinson’s disease, elevations in beta activity (13–35 Hz) in the subthalamic nucleus have been demonstrated to correlate with clinical impairment and have provided the basis for feedback control in trials of adaptive deep brain stimulation. These pilot studies have suggested that adaptive deep brain stimulation may potentially be more effective, efficient and selective than conventional deep brain stimulation, implying mechanistic differences between the two approaches. Here we test the hypothesis that such differences arise through differential effects on the temporal dynamics of beta activity. The latter is not constantly increased in Parkinson’s disease, but comes in bursts of different durations and amplitudes. We demonstrate that the amplitude of beta activity in the subthalamic nucleus increases in proportion to burst duration, consistent with progressively increasing synchronization. Effective adaptive deep brain stimulation truncated long beta bursts shifting the distribution of burst duration away from long duration with large amplitude towards short duration, lower amplitude bursts. Critically, bursts with shorter duration are negatively and bursts with longer duration positively correlated with the motor impairment off stimulation. Conventional deep brain stimulation did not change the distribution of burst durations. Although both adaptive and conventional deep brain stimulation suppressed mean beta activity amplitude compared to the unstimulated state, this was achieved by a selective effect on burst duration during adaptive deep brain stimulation, whereas conventional deep brain stimulation globally suppressed beta activity. We posit that the relatively selective effect of adaptive deep brain stimulation provides a rationale for why this

  16. The modulatory effect of adaptive deep brain stimulation on beta bursts in Parkinson's disease.

    PubMed

    Tinkhauser, Gerd; Pogosyan, Alek; Little, Simon; Beudel, Martijn; Herz, Damian M; Tan, Huiling; Brown, Peter

    2017-02-13

    Adaptive deep brain stimulation uses feedback about the state of neural circuits to control stimulation rather than delivering fixed stimulation all the time, as currently performed. In patients with Parkinson's disease, elevations in beta activity (13-35 Hz) in the subthalamic nucleus have been demonstrated to correlate with clinical impairment and have provided the basis for feedback control in trials of adaptive deep brain stimulation. These pilot studies have suggested that adaptive deep brain stimulation may potentially be more effective, efficient and selective than conventional deep brain stimulation, implying mechanistic differences between the two approaches. Here we test the hypothesis that such differences arise through differential effects on the temporal dynamics of beta activity. The latter is not constantly increased in Parkinson's disease, but comes in bursts of different durations and amplitudes. We demonstrate that the amplitude of beta activity in the subthalamic nucleus increases in proportion to burst duration, consistent with progressively increasing synchronization. Effective adaptive deep brain stimulation truncated long beta bursts shifting the distribution of burst duration away from long duration with large amplitude towards short duration, lower amplitude bursts. Critically, bursts with shorter duration are negatively and bursts with longer duration positively correlated with the motor impairment off stimulation. Conventional deep brain stimulation did not change the distribution of burst durations. Although both adaptive and conventional deep brain stimulation suppressed mean beta activity amplitude compared to the unstimulated state, this was achieved by a selective effect on burst duration during adaptive deep brain stimulation, whereas conventional deep brain stimulation globally suppressed beta activity. We posit that the relatively selective effect of adaptive deep brain stimulation provides a rationale for why this approach could

  17. Reversing cognitive–motor impairments in Parkinson’s disease patients using a computational modelling approach to deep brain stimulation programming

    PubMed Central

    Frankemolle, Anneke M. M.; Wu, Jennifer; Noecker, Angela M.; Voelcker-Rehage, Claudia; Ho, Jason C.; Vitek, Jerrold L.; McIntyre, Cameron C.

    2010-01-01

    Deep brain stimulation in the subthalamic nucleus is an effective and safe surgical procedure that has been shown to reduce the motor dysfunction of patients with advanced Parkinson’s disease. Bilateral subthalamic nucleus deep brain stimulation, however, has been associated with declines in cognitive and cognitive–motor functioning. It has been hypothesized that spread of current to nonmotor areas of the subthalamic nucleus may be responsible for declines in cognitive and cognitive–motor functioning. The aim of this study was to assess the cognitive–motor performance in advanced Parkinson’s disease patients with subthalamic nucleus deep brain stimulation parameters determined clinically (Clinical) to settings derived from a patient-specific computational model (Model). Data were collected from 10 patients with advanced Parkinson’s disease bilaterally implanted with subthalamic nucleus deep brain stimulation systems. These patients were assessed off medication and under three deep brain stimulation conditions: Off, Clinical or Model based stimulation. Clinical stimulation parameters had been determined based on clinical evaluations and were stable for at least 6 months prior to study participation. Model-based parameters were selected to minimize the spread of current to nonmotor portions of the subthalamic nucleus using Cicerone Deep Brain Stimulation software. For each stimulation condition, participants performed a working memory (n-back task) and motor task (force tracking) under single- and dual-task settings. During the dual-task, participants performed the n-back and force-tracking tasks simultaneously. Clinical and Model parameters were equally effective in improving the Unified Parkinson’s disease Rating Scale III scores relative to Off deep brain stimulation scores. Single-task working memory declines, in the 2-back condition, were significantly less under Model compared with Clinical deep brain stimulation settings. Under dual

  18. Unilateral subthalamic deep brain stimulation in advanced Parkinson's disease.

    PubMed

    Linazasoro, Gurutz; Van Blercom, Nadège; Lasa, Asier

    2003-06-01

    Eight patients with advanced PD received a unilateral STN DBS. The UPDRS III off drug-on DBS was improved by a mean 44%. Dyskinesias were ameliorated. Levodopa daily dose was reduced. Three patients required the implantation of the second electrode. Unilateral DBS may be efficacious in some patients with advanced PD. Copyright 2003 Movement Disorder Society

  19. Electrophysiological registration of phonological perception in the subthalamic nucleus of patients with Parkinson's Disease.

    PubMed

    De Letter, M; Aerts, A; Van Borsel, J; Vanhoutte, S; De Taeye, L; Raedt, R; van Mierlo, P; Boon, P; Van Roost, D; Santens, P

    2014-11-01

    Phonological processing is usually associated with the activation of cortical areas, especially in the left cerebral hemisphere. This study examined if phonologically elicited evoked potentials can be recorded directly from the subthalamic nucleus in patients with Parkinson's Disease (PD). Seven PD patients who had undergone implantation of deep brain electrodes for the stimulation of the subthalamic nucleus were included. Local field potentials were recorded in a pre-attentive auditory phonological task, an attentive auditory phonological discrimination task, and a word recognition task. Auditory evoked potentials related to phonological, but not lexical processing, could be demonstrated in the subthalamic nucleus for all three tasks. Only minor changes were found after levodopa administration. This study demonstrates that the subthalamic nucleus is involved in early phonological perception, which puts the subthalamic nucleus in a position to modify phonological perception in a larger cortico-subcortical network. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. [Functional imaging of deep brain stimulation in idiopathic Parkinson's disease].

    PubMed

    Hilker, R

    2010-10-01

    Functional brain imaging allows the effects of deep brain stimulation (DBS) on the living human brain to be investigated. In patients with advanced Parkinson's disease (PD), positron emission tomography (PET) studies were undertaken at rest as well as under motor, cognitive or behavioral activation. DBS leads to a reduction of abnormal PD-related network activity in the motor system, which partly correlates with the improvement of motor symptoms. The local increase of energy consumption within the direct target area suggests a predominant excitatory influence of the stimulation current on neuronal tissue. Remote effects of DBS of the subthalamic nucleus (STN) on frontal association cortices indicate an interference of stimulation energy with associative and limbic basal ganglia loops. Taken together, functional brain imaging provides very valuable data for advancement of the DBS technique in PD therapy.

  1. Deep Brain Stimulation

    PubMed Central

    Lyketsos, Constantine G.; Pendergrass, Jo Cara; Lozano, Andres M.

    2012-01-01

    Recent studies have identified an association between memory deficits and defects of the integrated neuronal cortical areas known collectively as the default mode network. It is conceivable that the amyloid deposition or other molecular abnormalities seen in patients with Alzheimer’s disease may interfere with this network and disrupt neuronal circuits beyond the localized brain areas. Therefore, Alzheimer’s disease may be both a degenerative disease and a broader system-level disorder affecting integrated neuronal pathways involved in memory. In this paper, we describe the rationale and provide some evidence to support the study of deep brain stimulation of the hippocampal fornix as a novel treatment to improve neuronal circuitry within these integrated networks and thereby sustain memory function in early Alzheimer’s disease. PMID:23346514

  2. Bibliometric profile of deep brain stimulation.

    PubMed

    Hu, Kejia; Moses, Ziev B; Xu, Wendong; Williams, Ziv

    2017-05-08

    We aimed to identify and analyze the characteristics of the 100 most highly-cited papers in the research field of deep brain stimulation (DBS). The Web of Science was searched for highly-cited papers related to DBS research. The number of citations, countries, institutions of origin, year of publication, and research area were noted and analyzed. The 100 most highly-cited articles had a mean of 304.15 citations. These accrued an average of 25.39 citations a year. The most represented target by far was the subthalamic nucleus (STN). These articles were published in 46 high-impact journals, with Brain (n = 10) topping the list. These articles came from 11 countries, with the USA contributing the most highly-cited articles (n = 29); however, it was the University of Toronto (n = 13) in Canada that was the institution with the most highly-cited studies. This study identified the 100 most highly-cited studies and highlighted a historical perspective on the progress in the field of DBS. These findings allow for the recognition of the most influential reports and provide useful information that can indicate areas requiring further investigation.

  3. Mechanism of Deep Brain Stimulation: Inhibition, Excitation, or Disruption?

    PubMed

    Chiken, Satomi; Nambu, Atsushi

    2016-06-01

    Deep brain stimulation (DBS), applying high-frequency electrical stimulation to deep brain structures, has now provided an effective therapeutic option for treatment of various neurological and psychiatric disorders. DBS targeting the internal segment of the globus pallidus, subthalamic nucleus, and thalamus is used to treat symptoms of movement disorders, such as Parkinson's disease, dystonia, and tremor. However, the mechanism underlying the beneficial effects of DBS remains poorly understood and is still under debate: Does DBS inhibit or excite local neuronal elements? In this short review, we would like to introduce our recent work on the physiological mechanism of DBS and propose an alternative explanation: DBS dissociates input and output signals, resulting in the disruption of abnormal information flow through the stimulation site. © The Author(s) 2015.

  4. Cortical effects of deep brain stimulation: implications for pathogenesis and treatment of Parkinson disease.

    PubMed

    Li, Qian; Qian, Zhong-Ming; Arbuthnott, Gordon W; Ke, Ya; Yung, Wing-Ho

    2014-01-01

    High-frequency electrical stimulation that targets the subthalamic nucleus has proved to be beneficial in alleviating the motor symptoms in many patients with Parkinson disease. The mechanism of action for this paradigm of deep brain stimulation is still not fully understood, and this is, in part, attributed to the fact that there are diverse cellular elements at the stimulation site that could bring about local and distal effects. Recent studies in both human and animal models strongly suggest that the activity in the cortex, especially in the motor cortical areas, is directly altered by deep brain stimulation by signals traveling in an antidromic fashion from the subthalamic nucleus. Herein, we discuss the evidence for this proposition, as well as the mechanism by which antidromic activation desynchronizes motor cortical activity. The implications of these new findings for the pathogenesis and treatment of Parkinson disease are highlighted.

  5. Modulation of metabolic brain networks after subthalamic gene therapy for Parkinson's disease.

    PubMed

    Feigin, Andrew; Kaplitt, Michael G; Tang, Chengke; Lin, Tanya; Mattis, Paul; Dhawan, Vijay; During, Matthew J; Eidelberg, David

    2007-12-04

    Parkinson's disease (PD) is characterized by elevated expression of an abnormal metabolic brain network that is reduced by clinically effective treatment. We used fluorodeoxyglucose (FDG) positron emission tomography (PET) to determine the basis for motor improvement in 12 PD patients receiving unilateral subthalamic nucleus (STN) infusion of an adenoassociated virus vector expressing glutamic acid decarboxylase (AAV-GAD). After gene therapy, we observed significant reductions in thalamic metabolism on the operated side as well as concurrent metabolic increases in ipsilateral motor and premotor cortical regions. Abnormal elevations in the activity of metabolic networks associated with motor and cognitive functioning in PD patients were evident at baseline. The activity of the motor-related network declined after surgery and persisted at 1 year. These network changes correlated with improved clinical disability ratings. By contrast, the activity of the cognition-related network did not change after gene transfer. This suggests that modulation of abnormal network activity underlies the clinical outcome observed after unilateral STN AAV-GAD gene therapy. Network biomarkers may be used as physiological assays in early-phase trials of experimental therapies for PD and other neurodegenerative disease.

  6. Deep Brain Stimulation in Parkinson's Disease

    PubMed Central

    Groiss, S. J.; Wojtecki, L.; Südmeyer, M.

    2009-01-01

    During the last 15 years deep brain stimulation (DBS) has been established as a highly-effective therapy for advanced Parkinson's disease (PD). Patient selection, stereotactic implantation, postoperative stimulator programming and patient care requires a multi-disciplinary team including movement disorders specialists in neurology and functional neurosurgery. To treat medically refractory levodopa-induced motor complications or resistant tremor the preferred target for high-frequency DBS is the subthalamic nucleus (STN). STN-DBS results in significant reduction of dyskinesias and dopaminergic medication, improvement of all cardinal motor symptoms with sustained long-term benefits, and significant improvement of quality of life when compared with best medical treatment. These benefits have to be weighed against potential surgery-related adverse events, device-related complications, and stimulus-induced side effects. The mean disease duration before initiating DBS in PD is currently about 13 years. It is presently investigated whether the optimal timing for implantation may be at an earlier disease-stage to prevent psychosocial decline and to maintain quality of life for a longer period of time. PMID:21180627

  7. Body weight gain and deep brain stimulation.

    PubMed

    Rieu, Isabelle; Derost, Philippe; Ulla, Miguel; Marques, Ana; Debilly, Bérangère; De Chazeron, Ingrid; Chéreau, Isabelle; Lemaire, Jean Jacques; Boirie, Yves; Llorca, Pierre Michel; Durif, Franck

    2011-11-15

    Deep brain stimulation (DBS) is a neurosurgical technique that has now been available for some 25 years. It is used in the treatment of various motor disorders, e.g. Parkinson's disease (PD), essential tremor and dystonia, and neuropsychiatric illnesses, e.g. obsessive-compulsive disorder and Tourette syndrome. The surgical targets of DBS include the thalamic ventralis intermedius nucleus (Vim), the globus pallidus internus (GPi) and more recently the subthalamic nucleus (STN), currently considered as the reference target in the treatment of PD. In the last ten years, most studies in PD patients have described a rapid and marked weight gain in the months following DBS of the STN. This weight gain sometimes induces obesity and can have metabolic repercussions. The physiopathological mechanisms responsible for the weight gain are multifactorial (changes in energy metabolism and eating behaviour, reduction of motor complications, etc.). This review reports current knowledge concerning weight changes in patients treated by DBS with different surgical targets. It also describes the mechanisms responsible for weight gain and the health outcome for the patients.

  8. [Abscess at the implant site following apical parodontitis. Hardware-related complications of deep brain stimulation].

    PubMed

    Sixel-Döring, F; Trenkwalder, C; Kappus, C; Hellwig, D

    2006-08-01

    Deep brain stimulation of the subthalamic nucleus is an important treatment option for advanced stages of idiopathic Parkinson's disease, leading to significant improvement of motor symptoms in suited patients. Hardware-related complications such as technical malfunction, skin erosion, and infections however cause patient discomfort and additional expense. The patient presented here suffered a putrid infection of the impulse generator site following only local dental treatment of apical parodontitis. Therefore, prophylactic systemic antibiotic treatment is recommended for patients with implanted deep brain stimulation devices in case of operations, dental procedures, or infectious disease.

  9. Deep-brain-stimulation does not impair deglutition in Parkinson's disease.

    PubMed

    Lengerer, Sabrina; Kipping, Judy; Rommel, Natalie; Weiss, Daniel; Breit, Sorin; Gasser, Thomas; Plewnia, Christian; Krüger, Rejko; Wächter, Tobias

    2012-08-01

    A large proportion of patients with Parkinson's disease develop dysphagia during the course of the disease. Dysphagia in Parkinson's disease affects different phases of deglutition, has a strong impact on quality of life and may cause severe complications, i.e., aspirational pneumonia. So far, little is known on how deep-brain-stimulation of the subthalamic nucleus influences deglutition in PD. Videofluoroscopic swallowing studies on 18 patients with Parkinson's disease, which had been performed preoperatively, and postoperatively with deep-brain-stimulation-on and deep-brain-stimulation-off, were analyzed retrospectively. The patients were examined in each condition with three consistencies (viscous, fluid and solid). The 'New Zealand index for multidisciplinary evaluation of swallowing (NZIMES) Subscale One' for qualitative and 'Logemann-MBS-Parameters' for quantitative evaluation were assessed. Preoperatively, none of the patients presented with clinically relevant signs of dysphagia. While postoperatively, the mean daily levodopa equivalent dosage was reduced by 50% and deep-brain-stimulation led to a 50% improvement in motor symptoms measured by the UPDRS III, no clinically relevant influence of deep-brain-stimulation-on swallowing was observed using qualitative parameters (NZIMES). However quantitative parameters (Logemann scale) found significant changes of pharyngeal parameters with deep-brain-stimulation-on as compared to preoperative condition and deep-brain-stimulation-off mostly with fluid consistency. In Parkinson patients without dysphagia deep-brain-stimulation of the subthalamic nucleus modulates the pharyngeal deglutition phase but has no clinically relevant influence on deglutition. Further studies are needed to test if deep-brain-stimulation is a therapeutic option for patients with swallowing disorders. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Modulation of motor inhibition by subthalamic stimulation in obsessive-compulsive disorder

    PubMed Central

    Kibleur, A; Gras-Combe, G; Benis, D; Bastin, J; Bougerol, T; Chabardès, S; Polosan, M; David, O

    2016-01-01

    High-frequency deep brain stimulation of the subthalamic nucleus can be used to treat severe obsessive-compulsive disorders that are refractory to conventional treatments. The mechanisms of action of this approach possibly rely on the modulation of associative-limbic subcortical–cortical loops, but remain to be fully elucidated. Here in 12 patients, we report the effects of high-frequency stimulation of the subthalamic nucleus on behavior, and on electroencephalographic responses and inferred effective connectivity during motor inhibition processes involved in the stop signal task. First, we found that patients were faster to respond and had slower motor inhibition processes when stimulated. Second, the subthalamic stimulation modulated the amplitude and delayed inhibition-related electroencephalographic responses. The power of reconstructed cortical current densities decreased in the stimulation condition in a parietal–frontal network including cortical regions of the inhibition network such as the superior parts of the inferior frontal gyri and the dorsolateral prefrontal cortex. Finally, dynamic causal modeling revealed that the subthalamic stimulation was more likely to modulate efferent connections from the basal ganglia, modeled as a hidden source, to the cortex. The connection from the basal ganglia to the right inferior frontal gyrus was significantly decreased by subthalamic stimulation. Beyond motor inhibition, our study thus strongly suggests that the mechanisms of action of high-frequency subthalamic stimulation are not restricted to the subthalamic nucleus, but also involve the modulation of distributed subcortical–cortical networks. PMID:27754484

  11. Differential effects of deep brain stimulation on verbal fluency.

    PubMed

    Ehlen, Felicitas; Schoenecker, Thomas; Kühn, Andrea A; Klostermann, Fabian

    2014-07-01

    We aimed at gaining insights into principles of subcortical lexical processing. Therefore, effects of deep brain stimulation (DBS) in different target structures on verbal fluency (VF) were tested. VF was assessed with active vs. inactivated DBS in 13 and 14 patients with DBS in the vicinity of the thalamic ventral intermediate nucleus (VIM) and, respectively, of the subthalamic nucleus (STN). Results were correlated to electrode localizations in postoperative MRI, and compared to those of 12 age-matched healthy controls. Patients' VF performance was generally below normal. However, while activation of DBS in the vicinity of VIM provoked marked VF decline, it induced subtle phonemic VF enhancement in the vicinity of STN. The effects correlated with electrode localizations in left hemispheric stimulation sites. The results show distinct dependencies of VF on DBS in the vicinity of VIM vs. STN. Particular risks for deterioration occur in patients with relatively ventromedial thalamic electrodes. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Historical developments in children's deep brain stimulation.

    PubMed

    Cif, Laura; Coubes, Philippe

    2017-01-01

    Heterogeneous by the underlying pathobiology and clinical presentation, childhood onset dystonia is most frequently progressive, with related disability and limitations in functions of daily living. Consequently, there is an obvious need for efficient symptomatic therapies. Following lesional surgery to basal ganglia (BG) and thalamus, deep brain stimulation (DBS) is a more conservative and adjustable intervention to and validated for internal segment of the globus pallidus (GPi), highly efficient in treating isolated "primary" dystonia and associated symptoms such as subcortical myoclonus. The role of DBS in acquired, neurometabolic and degenerative disorders with dystonia deserves further exploration to confirm as an efficient and lasting therapy. However, the pathobiological background with distribution of the sequellae over the central nervous system and related clinical features, will limit DBS efficacy in these conditions. Cumulative arguments propose DBS in severe life threatening dystonic conditions called status dystonicus as first line therapy, irrespective of the underlying cause. There are no currently available validated selection criteria for DBS in pediatric dystonia. Concurrent targets such as subthalamic nucleus (STN) and several motor nuclei of the thalamus are under exploration and only little information is available in children. DBS programming in paediatric population was adopted from experience in adults. The choice of neuromodulatory DBS parameters could influence not only the initial therapeutic outcome of dystonic symptoms but also its maintenance over time and potentially the occurrence of DBS related side effects. DBS allows efficient symptomatic treatment of severe dystonia in children and advances pathophysiological knowledge about local and distributed abnormal neural activity over the motor cortical-subcortical networks in dystonia and other movement disorders. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights

  13. Deep brain stimulation

    MedlinePlus

    ... the brain The neurostimulator, which puts out the electric current. The stimulator is similar to a heart pacemaker . It is usually placed under the skin near the collarbone, but may be ... pulses travel from the neurostimulator, along the extension ...

  14. Neural correlates of lexical decisions in Parkinson's disease revealed with multivariate extraction of cortico-subthalamic interactions.

    PubMed

    Hohlefeld, F U; Ewald, A; Ehlen, F; Tiedt, H O; Horn, A; Kühn, A A; Curio, G; Klostermann, F; Nikulin, V V

    2017-04-01

    Neural interactions between cortex and basal ganglia are pivotal for sensorimotor processing. Specifically, coherency between cortex and subthalamic structures is a frequently studied phenomenon in patients with Parkinson's disease. However, it is unknown whether cortico-subthalamic coherency might also relate to cognitive aspects of task performance, e.g., language processing. Furthermore, standard coherency studies are challenged by how to efficiently handle multi-channel recordings. In eight patients with Parkinson's disease treated with deep brain stimulation, simultaneous recordings of surface electroencephalography and deep local field potentials were obtained from bilateral subthalamic nuclei, during performing a lexical decision task. A recent multivariate coherency measure (maximized imaginary part of coherency, MIC) was applied, simultaneously accounting for multi-channel recordings. Cortico-subthalamic synchronization (MIC) in 14-35Hz oscillations positively correlated with accuracy in lexical decisions across patients, but not in 7-13Hz oscillations. In contrast to multivariate MIC, no significant correlation was obtained when extracting cortico-subthalamic synchronization by "standard" bivariate coherency. Cortico-subthalamic synchronization may relate to non-motor aspects of task performance, here reflected in lexical accuracy. The results tentatively suggest the relevance of cortico-subthalamic interactions for lexical decisions. Multivariate coherency might be effective to extract neural synchronization from multi-channel recordings. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  15. Freezing and hypokinesia of gait induced by stimulation of the subthalamic region.

    PubMed

    Tommasi, Giorgio; Lopiano, Leonardo; Zibetti, Maurizio; Cinquepalmi, Annina; Fronda, Chiara; Bergamasco, Bruno; Ducati, Alessandro; Lanotte, Michele

    2007-07-15

    We report a case of a Parkinson's disease patient treated by bilateral deep brain stimulation of the subthalamic nucleus, who developed freezing and hypokinesia of gait induced by stimulation through a left-side misplaced electrode which was more antero-medial than the planned trajectory. Subsequently, correct repositioning of the left electrode afforded complete relief of gait disturbances. Freezing and hypokinesia of gait may be side effects of deep brain stimulation of the subthalamic region due to current spreading antero-medially to the subthalamic nucleus. These side effects are not subject to habituation and restrict any increase in stimulation parameters. We hypothesize that pallidal projections to the pedunculopontine nucleus could be responsible for these gait disturbances in our patient.

  16. Deep brain stimulation for the treatment of uncommon tremor syndromes.

    PubMed

    Ramirez-Zamora, Adolfo; Okun, Michael S

    2016-08-01

    Deep brain stimulation (DBS) has become a standard therapy for the treatment of select cases of medication refractory essential tremor and Parkinson's disease however the effectiveness and long-term outcomes of DBS in other uncommon and complex tremor syndromes has not been well established. Traditionally, the ventralis intermedius nucleus (VIM) of the thalamus has been considered the main target for medically intractable tremors; however alternative brain regions and improvements in stereotactic techniques and hardware may soon change the horizon for treatment of complex tremors. In this article, we conducted a PubMed search using different combinations between the terms 'Uncommon tremors', 'Dystonic tremor', 'Holmes tremor' 'Midbrain tremor', 'Rubral tremor', 'Cerebellar tremor', 'outflow tremor', 'Multiple Sclerosis tremor', 'Post-traumatic tremor', 'Neuropathic tremor', and 'Deep Brain Stimulation/DBS'. Additionally, we examined and summarized the current state of evolving interventions for treatment of complex tremor syndromes. Expert commentary: Recently reported interventions for rare tremors include stimulation of the posterior subthalamic area, globus pallidus internus, ventralis oralis anterior/posterior thalamic subnuclei, and the use of dual lead stimulation in one or more of these targets. Treatment should be individualized and dictated by tremor phenomenology and associated clinical features.

  17. Deep brain stimulation for the treatment of uncommon tremor syndromes

    PubMed Central

    Ramirez-Zamora, Adolfo; Okun, Michael S.

    2016-01-01

    ABSTRACT Introduction: Deep brain stimulation (DBS) has become a standard therapy for the treatment of select cases of medication refractory essential tremor and Parkinson’s disease however the effectiveness and long-term outcomes of DBS in other uncommon and complex tremor syndromes has not been well established. Traditionally, the ventralis intermedius nucleus (VIM) of the thalamus has been considered the main target for medically intractable tremors; however alternative brain regions and improvements in stereotactic techniques and hardware may soon change the horizon for treatment of complex tremors. Areas covered: In this article, we conducted a PubMed search using different combinations between the terms ‘Uncommon tremors’, ‘Dystonic tremor’, ‘Holmes tremor’ ‘Midbrain tremor’, ‘Rubral tremor’, ‘Cerebellar tremor’, ‘outflow tremor’, ‘Multiple Sclerosis tremor’, ‘Post-traumatic tremor’, ‘Neuropathic tremor’, and ‘Deep Brain Stimulation/DBS’. Additionally, we examined and summarized the current state of evolving interventions for treatment of complex tremor syndromes. Expert c ommentary: Recently reported interventions for rare tremors include stimulation of the posterior subthalamic area, globus pallidus internus, ventralis oralis anterior/posterior thalamic subnuclei, and the use of dual lead stimulation in one or more of these targets. Treatment should be individualized and dictated by tremor phenomenology and associated clinical features. PMID:27228280

  18. Low-frequency deep brain stimulation for Parkinson's disease: Great expectation or false hope?

    PubMed

    di Biase, Lazzaro; Fasano, Alfonso

    2016-07-01

    The long-term efficacy of subthalamic deep brain stimulation for Parkinson's disease is not always retained, and many patients lose the improvement achieved during the "second honeymoon" following surgery. Deep brain stimulation is a versatile tool, as stimulation parameters may undergo a fine-tuning depending on clinical needs. Among them, frequency is the parameter that leads to more complex scenarios because there is no generalizable relationship between its modulation and the overall clinical response, which also depends on the specific considered sign. High-frequency stimulation (>100 Hz) has shown to be effective in improving most parkinsonian signs, particularly the levodopa-responsive ones. However, its effect on axial signs (such as balance, gait, speech, or swallowing) may not be sustained, minimal, or even detrimental. For these reasons, several studies have explored the effectiveness of low-frequency stimulation (generally 60 or 80 Hz). Methods, results, and especially interpretations of these studies are quite variable. Although the use of low-frequency stimulation certainly opens new avenues in the field of deep brain stimulation, after having gathered all the available evidence in patients with subthalamic implants, our conclusion is that it might be clinically useful mainly when it lessens the detrimental effects of high-frequency stimulation. © 2016 International Parkinson and Movement Disorder Society.

  19. Decisional impulsivity and the associative-limbic subthalamic nucleus in obsessive-compulsive disorder: stimulation and connectivity.

    PubMed

    Voon, Valerie; Droux, Fabien; Morris, Laurel; Chabardes, Stephan; Bougerol, Thierry; David, Olivier; Krack, Paul; Polosan, Mircea

    2017-02-01

    Why do we make hasty decisions for short-term gain? Rapid decision-making with limited accumulation of evidence and delay discounting are forms of decisional impulsivity. The subthalamic nucleus is implicated in inhibitory function but its role in decisional impulsivity is less well-understood. Here we assess decisional impulsivity in subjects with obsessive compulsive disorder who have undergone deep brain stimulation of the limbic and associative subthalamic nucleus. We show that stimulation of the subthalamic nucleus is causally implicated in increasing decisional impulsivity with less accumulation of evidence during probabilistic uncertainty and in enhancing delay discounting. Subthalamic stimulation shifts evidence accumulation in subjects with obsessive-compulsive disorder towards a functional less cautious style closer to that of healthy controls emphasizing its adaptive nature. Thus, subjects with obsessive compulsive disorder on subthalamic stimulation may be less likely to check for evidence (e.g. checking that the stove is on) with no difference in subjective confidence (or doubt). In a separate study, we replicate in humans (154 healthy controls) using resting state functional connectivity, tracing studies conducted in non-human primates dissociating limbic, associative and motor frontal hyper-direct connectivity with anterior and posterior subregions of the subthalamic nucleus. We show lateralization of functional connectivity of bilateral ventral striatum to right anterior ventromedial subthalamic nucleus consistent with previous observations of lateralization of emotionally evoked activity to right ventral subthalamic nucleus. We use a multi-echo sequence with independent components analysis, which has been shown to have enhanced signal-to-noise ratio, thus optimizing visualization of small subcortical structures. These findings in healthy controls converge with the effective contacts in obsessive compulsive disorder patients localized within the

  20. Pallidal deep brain stimulation relieves camptocormia in primary dystonia.

    PubMed

    Hagenacker, Tim; Gerwig, Marcus; Gasser, Thomas; Miller, Dorothea; Kastrup, Oliver; Jokisch, Daniel; Sure, Ulrich; Frings, Markus

    2013-07-01

    Camptocormia, characterised by a forward flexion of the thoracolumbar spine may occur in various movement disorders, mainly in Parkinson's disease or in primary dystonia. In severe cases, patients with camptocormia are unable to walk. While treatment options are limited, deep brain stimulation (DBS) with bilateral stimulation of the subthalamic nucleus or globus pallidus internus (GPi) has been proposed as a therapeutic option in refractory cases of Parkinson's disease. Here we present two patients with severe camptocormia as an isolated form of dystonia and as part of generalised dystonia, respectively, which were both treated with bilateral stimulation of the GPi. Symptoms of dystonia were assessed using the Burke-Fahn-Marsden dystonia rating scale (BFM) before and during deep brain stimulation. In both patients there was a significant functional improvement following long-term bilateral GPi stimulation and both patients gained ability to walk. In the first patient with an isolated dystonic camptocormia the BFM motor subscore for the truncal flexion improved by 75 %. The total BFM motor score in the second patient with a camptocormia in generalised dystonia improved by 45 %, while the BFM score for truncal flexion improved by 87 %. In both patients the effect of the bilateral GPi stimulation on camptocormia was substantial, independent of generalisation of dystonia. Therefore, GPi DBS is a possible treatment option for this rare disease.

  1. High incidence of carpal tunnel syndrome after deep brain stimulation in Parkinson's disease.

    PubMed

    Loizon, Marine; Laurencin, Chloé; Vial, Christophe; Danaila, Teodor; Thobois, Stéphane

    2016-12-01

    We observed several cases of carpal tunnel syndrome (CTS) revealed after subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD). 115 consecutive PD patients who underwent STN-DBS between 2010 and 2014 at the Neurological Hospital in Lyon were retrospectively included. CTS was accepted as the diagnosis only if clinical examination and ENMG both confirmed it. Nine patients (7.8 %) developed CTS in the 2 years following surgery, which is far beyond the 2.7/1000 incidence in the general population. The present study shows an overrepresentation of CTS occurrence after STN-DBS in PD.

  2. Predicting acute affective symptoms after deep brain stimulation surgery in Parkinson's disease.

    PubMed

    Schneider, Frank; Reske, Martina; Finkelmeyer, Andreas; Wojtecki, Lars; Timmermann, Lars; Brosig, Timo; Backes, Volker; Amir-Manavi, Atoosa; Sturm, Volker; Habel, Ute; Schnitzler, Alfons

    2010-01-01

    The current study aimed to investigate predictive markers for acute symptoms of depression and mania following deep brain stimulation (DBS) surgery of the subthalamic nucleus for the treatment of motor symptoms in Parkinson's disease (PD). Fourteen patients with PD (7 males) were included in a prospective longitudinal study. Neuropsychological tests, psychopathology scales and tests of motor functions were administered at several time points prior to and after neurosurgery. Pre-existing psychopathological and motor symptoms predicted postoperative affective side effects of DBS surgery. As these can easily be assessed, they should be considered along with other selection criteria for DBS surgery.

  3. Deep brain stimulation and continuous dopaminergic stimulation in advanced Parkinson's disease.

    PubMed

    Wolters, Erik Ch

    2007-09-01

    Patients receiving oral levodopa, the standard treatment for Parkinson's disease (PD), eventually develop motor fluctuations and dyskinesias. Treatment options for patients with these symptoms include high-frequency deep brain stimulation of the subthalamic nucleus (STN-DBS) or continuous dopaminergic stimulation (CDS). STN-DBS is the prevalent surgical therapy for PD and has shown efficacy, but behavioural disorders, including cognitive problems, depression and suicidality have been reported. CDS can be achieved with oral dopamine agonists with a long half-life, transdermal or subcutaneous delivery of dopamine agonists, or intestinal levodopa infusion. Of these, duodenal levodopa infusion appears to be the most promising option in terms of both efficacy and safety.

  4. Subthalamic nucleus stimulation and somatosensory temporal discrimination in Parkinson's disease.

    PubMed

    Conte, Antonella; Modugno, Nicola; Lena, Francesco; Dispenza, Sabrina; Gandolfi, Barbara; Iezzi, Ennio; Fabbrini, Giovanni; Berardelli, Alfredo

    2010-09-01

    Whereas numerous studies document the effects of dopamine medication and deep brain stimulation on motor function in patients with Parkinson's disease, few have investigated deep brain stimulation-induced changes in sensory functions. In this study of 13 patients with Parkinson's disease, we tested the effects of deep brain stimulation on the somatosensory temporal discrimination threshold. To investigate whether deep brain stimulation and dopaminergic medication induce similar changes in somatosensory discrimination, somatosensory temporal discrimination threshold values were acquired under four experimental conditions: (i) medication ON/deep brain stimulation on; (ii) medication ON/deep brain stimulation off; (iii) medication OFF/deep brain stimulation on; and (iv) medication OFF/deep brain stimulation off. Patients also underwent clinical and neuropsychological evaluations during each experimental session. Somatosensory temporal discrimination threshold values obtained in patients were compared with 13 age-matched healthy subjects. Somatosensory temporal discrimination threshold values were significantly higher in patients than in healthy subjects. In patients, somatosensory temporal discrimination threshold values were significantly lower when patients were studied in medication ON than in medication OFF conditions. Somatosensory temporal discrimination threshold values differed significantly between deep brain stimulation on and deep brain stimulation off conditions only when the patients were studied in the medication ON condition and were higher in the deep brain stimulation on/medication ON than in the deep brain stimulation off/medication ON condition. Dopamine but not subthalamic nucleus deep brain stimulation restores the altered somatosensory temporal discrimination in patients with Parkinson's disease. Deep brain stimulation degrades somatosensory temporal discrimination by modifying central somatosensory processing whereas dopamine restores the

  5. Patient-Specific Model-Based Investigation of Speech Intelligibility and Movement during Deep Brain Stimulation

    PubMed Central

    Åström, Mattias; Tripoliti, Elina; Hariz, Marwan I.; Zrinzo, Ludvic U.; Martinez-Torres, Irene; Limousin, Patricia; Wårdell, Karin

    2010-01-01

    Background/Aims Deep brain stimulation (DBS) is widely used to treat motor symptoms in patients with advanced Parkinson's disease. The aim of this study was to investigate the anatomical aspects of the electric field in relation to effects on speech and movement during DBS in the subthalamic nucleus. Methods Patient-specific finite element models of DBS were developed for simulation of the electric field in 10 patients. In each patient, speech intelligibility and movement were assessed during 2 electrical settings, i.e. 4 V (high) and 2 V (low). The electric field was simulated for each electrical setting. Results Movement was improved in all patients for both high and low electrical settings. In general, high-amplitude stimulation was more consistent in improving the motor scores than low-amplitude stimulation. In 6 cases, speech intelligibility was impaired during high-amplitude electrical settings. Stimulation of part of the fasciculus cerebellothalamicus from electrodes positioned medial and/or posterior to the center of the subthalamic nucleus was recognized as a possible cause of the stimulation-induced dysarthria. Conclusion Special attention to stimulation-induced speech impairments should be taken in cases when active electrodes are positioned medial and/or posterior to the center of the subthalamic nucleus. PMID:20460952

  6. Patient-specific model-based investigation of speech intelligibility and movement during deep brain stimulation.

    PubMed

    Aström, Mattias; Tripoliti, Elina; Hariz, Marwan I; Zrinzo, Ludvic U; Martinez-Torres, Irene; Limousin, Patricia; Wårdell, Karin

    2010-01-01

    Deep brain stimulation (DBS) is widely used to treat motor symptoms in patients with advanced Parkinson's disease. The aim of this study was to investigate the anatomical aspects of the electric field in relation to effects on speech and movement during DBS in the subthalamic nucleus. Patient-specific finite element models of DBS were developed for simulation of the electric field in 10 patients. In each patient, speech intelligibility and movement were assessed during 2 electrical settings, i.e. 4 V (high) and 2 V (low). The electric field was simulated for each electrical setting. Movement was improved in all patients for both high and low electrical settings. In general, high-amplitude stimulation was more consistent in improving the motor scores than low-amplitude stimulation. In 6 cases, speech intelligibility was impaired during high-amplitude electrical settings. Stimulation of part of the fasciculus cerebellothalamicus from electrodes positioned medial and/or posterior to the center of the subthalamic nucleus was recognized as a possible cause of the stimulation-induced dysarthria. Special attention to stimulation-induced speech impairments should be taken in cases when active electrodes are positioned medial and/or posterior to the center of the subthalamic nucleus. 2010 S. Karger AG, Basel.

  7. Impact of deep brain stimulation on upper limb akinesia in Parkinson's disease.

    PubMed

    Brown, R G; Dowsey, P L; Brown, P; Jahanshahi, M; Pollak, P; Benabid, A L; Rodriguez-Oroz, M C; Obeso, J; Rothwell, J C

    1999-04-01

    Recent pathophysiological models of Parkinson's disease have led to new surgical approaches to treatment including deep brain stimulation (DBS) and lesioning of basal ganglia structures. Various measures of upper limb akinesia were assessed in 6 patients with bilateral DBS of the internal pallidum and 6 with DBS of the subthalamic nucleus. Stimulation improved a number of aspects of motor function, and particularly movement time, and force production. Time to initiate movements, and to perform repetitive movements also improved but less dramatically. Processes indicating preparatory motor processes showed no significant change. Few significant differences were found between the internal pallidum and subthalamic nucleus groups. In general, the effects of DBS closely parallel previous reports of the effects of dopaminergic medication. It is suggested that disrupted pallidal output in Parkinson's disease interferes with the rate, level, and coordination of force production but has little effect on preparatory processes. The similarity of the effects of subthalamic nucleus and internal pallidum stimulation suggests this disrupted outflow is the most important determinant of upper limb akinesia in Parkinson's disease. The effects of DBS were similar to the effects of unilateral pallidal lesions reported elsewhere.

  8. Deep Brain Stimulation: Expanding Applications

    PubMed Central

    TEKRIWAL, Anand; BALTUCH, Gordon

    2015-01-01

    For over two decades, deep brain stimulation (DBS) has shown significant efficacy in treatment for refractory cases of dyskinesia, specifically in cases of Parkinson's disease and dystonia. DBS offers potential alleviation from symptoms through a well-tolerated procedure that allows personalized modulation of targeted neuroanatomical regions and related circuitries. For clinicians contending with how to provide patients with meaningful alleviation from often debilitating intractable disorders, DBSs titratability and reversibility make it an attractive treatment option for indications ranging from traumatic brain injury to progressive epileptic supra-synchrony. The expansion of our collective knowledge of pathologic brain circuitries, as well as advances in imaging capabilities, electrophysiology techniques, and material sciences have contributed to the expanding application of DBS. This review will examine the potential efficacy of DBS for neurologic and psychiatric disorders currently under clinical investigation and will summarize findings from recent animal models. PMID:26466888

  9. Decisional impulsivity and the associative-limbic subthalamic nucleus in obsessive-compulsive disorder: stimulation and connectivity

    PubMed Central

    Droux, Fabien; Morris, Laurel; Chabardes, Stephan; Bougerol, Thierry; David, Olivier; Krack, Paul; Polosan, Mircea

    2017-01-01

    Why do we make hasty decisions for short-term gain? Rapid decision-making with limited accumulation of evidence and delay discounting are forms of decisional impulsivity. The subthalamic nucleus is implicated in inhibitory function but its role in decisional impulsivity is less well-understood. Here we assess decisional impulsivity in subjects with obsessive compulsive disorder who have undergone deep brain stimulation of the limbic and associative subthalamic nucleus. We show that stimulation of the subthalamic nucleus is causally implicated in increasing decisional impulsivity with less accumulation of evidence during probabilistic uncertainty and in enhancing delay discounting. Subthalamic stimulation shifts evidence accumulation in subjects with obsessive-compulsive disorder towards a functional less cautious style closer to that of healthy controls emphasizing its adaptive nature. Thus, subjects with obsessive compulsive disorder on subthalamic stimulation may be less likely to check for evidence (e.g. checking that the stove is on) with no difference in subjective confidence (or doubt). In a separate study, we replicate in humans (154 healthy controls) using resting state functional connectivity, tracing studies conducted in non-human primates dissociating limbic, associative and motor frontal hyper-direct connectivity with anterior and posterior subregions of the subthalamic nucleus. We show lateralization of functional connectivity of bilateral ventral striatum to right anterior ventromedial subthalamic nucleus consistent with previous observations of lateralization of emotionally evoked activity to right ventral subthalamic nucleus. We use a multi-echo sequence with independent components analysis, which has been shown to have enhanced signal-to-noise ratio, thus optimizing visualization of small subcortical structures. These findings in healthy controls converge with the effective contacts in obsessive compulsive disorder patients localized within the

  10. Automated 3-Dimensional Brain Atlas Fitting to Microelectrode Recordings from Deep Brain Stimulation Surgeries

    PubMed Central

    Luján, J. Luis; Noecker, Angela M.; Butson, Christopher R.; Cooper, Scott E.; Walter, Benjamin L.; Vitek, Jerrold L.; McIntyre, Cameron C.

    2009-01-01

    Objective Deep brain stimulation (DBS) surgeries commonly rely on brain atlases and microelectrode recordings (MER) to help identify the target location for electrode implantation. We present an automated method for optimally fitting a 3-dimensional brain atlas to intraoperative MER and predicting a target DBS electrode location in stereotactic coordinates for the patient. Methods We retrospectively fit a 3-dimensional brain atlas to MER points from 10 DBS surgeries targeting the subthalamic nucleus (STN). We used a constrained optimization algorithm to maximize the MER points correctly fitted (i.e., contained) within the appropriate atlas nuclei. We compared our optimization approach to conventional anterior commissure-posterior commissure (AC/PC) scaling, and to manual fits performed by four experts. A theoretical DBS electrode target location in the dorsal STN was customized to each patient as part of the fitting process and compared to the location of the clinically defined therapeutic stimulation contact. Results The human expert and computer optimization fits achieved significantly better fits than the AC/PC scaling (80, 81, and 41% of correctly fitted MER, respectively). However, the optimization fits were performed in less time than the expert fits and converged to a single solution for each patient, eliminating interexpert variance. Conclusions and Significance DBS therapeutic outcomes are directly related to electrode implantation accuracy. Our automated fitting techniques may aid in the surgical decision-making process by optimally integrating brain atlas and intraoperative neurophysiological data to provide a visual guide for target identification. PMID:19556832

  11. Elastic and viscoelastic mechanical properties of brain tissues on the implanting trajectory of sub-thalamic nucleus stimulation.

    PubMed

    Li, Yan; Deng, Jianxin; Zhou, Jun; Li, Xueen

    2016-11-01

    Corresponding to pre-puncture and post-puncture insertion, elastic and viscoelastic mechanical properties of brain tissues on the implanting trajectory of sub-thalamic nucleus stimulation are investigated, respectively. Elastic mechanical properties in pre-puncture are investigated through pre-puncture needle insertion experiments using whole porcine brains. A linear polynomial and a second order polynomial are fitted to the average insertion force in pre-puncture. The Young's modulus in pre-puncture is calculated from the slope of the two fittings. Viscoelastic mechanical properties of brain tissues in post-puncture insertion are investigated through indentation stress relaxation tests for six interested regions along a planned trajectory. A linear viscoelastic model with a Prony series approximation is fitted to the average load trace of each region using Boltzmann hereditary integral. Shear relaxation moduli of each region are calculated using the parameters of the Prony series approximation. The results show that, in pre-puncture insertion, needle force almost increases linearly with needle displacement. Both fitting lines can perfectly fit the average insertion force. The Young's moduli calculated from the slope of the two fittings are worthy of trust to model linearly or nonlinearly instantaneous elastic responses of brain tissues, respectively. In post-puncture insertion, both region and time significantly affect the viscoelastic behaviors. Six tested regions can be classified into three categories in stiffness. Shear relaxation moduli decay dramatically in short time scales but equilibrium is never truly achieved. The regional and temporal viscoelastic mechanical properties in post-puncture insertion are valuable for guiding probe insertion into each region on the implanting trajectory.

  12. In vivo impedance spectroscopy of deep brain stimulation electrodes.

    PubMed

    Lempka, Scott F; Miocinovic, Svjetlana; Johnson, Matthew D; Vitek, Jerrold L; McIntyre, Cameron C

    2009-08-01

    Deep brain stimulation (DBS) represents a powerful clinical technology, but a systematic characterization of the electrical interactions between the electrode and the brain is lacking. The goal of this study was to examine the in vivo changes in the DBS electrode impedance that occur after implantation and during clinically relevant stimulation. Clinical DBS devices typically apply high-frequency voltage-controlled stimulation, and as a result, the injected current is directly regulated by the impedance of the electrode-tissue interface. We monitored the impedance of scaled-down clinical DBS electrodes implanted in the thalamus and subthalamic nucleus of a rhesus macaque using electrode impedance spectroscopy (EIS) measurements ranging from 0.5 Hz to 10 kHz. To further characterize our measurements, equivalent circuit models of the electrode-tissue interface were used to quantify the role of various interface components in producing the observed electrode impedance. Following implantation, the DBS electrode impedance increased and a semicircular arc was observed in the high-frequency range of the EIS measurements, commonly referred to as the tissue component of the impedance. Clinically relevant stimulation produced a rapid decrease in electrode impedance with extensive changes in the tissue component. These post-operative and stimulation-induced changes in impedance could play an important role in the observed functional effects of voltage-controlled DBS and should be considered during clinical stimulation parameter selection and chronic animal research studies.

  13. Probabilistic analysis of activation volumes generated during deep brain stimulation.

    PubMed

    Butson, Christopher R; Cooper, Scott E; Henderson, Jaimie M; Wolgamuth, Barbara; McIntyre, Cameron C

    2011-02-01

    Deep brain stimulation (DBS) is an established therapy for the treatment of Parkinson's disease (PD) and shows great promise for the treatment of several other disorders. However, while the clinical analysis of DBS has received great attention, a relative paucity of quantitative techniques exists to define the optimal surgical target and most effective stimulation protocol for a given disorder. In this study we describe a methodology that represents an evolutionary addition to the concept of a probabilistic brain atlas, which we call a probabilistic stimulation atlas (PSA). We outline steps to combine quantitative clinical outcome measures with advanced computational models of DBS to identify regions where stimulation-induced activation could provide the best therapeutic improvement on a per-symptom basis. While this methodology is relevant to any form of DBS, we present example results from subthalamic nucleus (STN) DBS for PD. We constructed patient-specific computer models of the volume of tissue activated (VTA) for 163 different stimulation parameter settings which were tested in six patients. We then assigned clinical outcome scores to each VTA and compiled all of the VTAs into a PSA to identify stimulation-induced activation targets that maximized therapeutic response with minimal side effects. The results suggest that selection of both electrode placement and clinical stimulation parameter settings could be tailored to the patient's primary symptoms using patient-specific models and PSAs.

  14. In vivo impedance spectroscopy of deep brain stimulation electrodes

    NASA Astrophysics Data System (ADS)

    Lempka, Scott F.; Miocinovic, Svjetlana; Johnson, Matthew D.; Vitek, Jerrold L.; McIntyre, Cameron C.

    2009-08-01

    Deep brain stimulation (DBS) represents a powerful clinical technology, but a systematic characterization of the electrical interactions between the electrode and the brain is lacking. The goal of this study was to examine the in vivo changes in the DBS electrode impedance that occur after implantation and during clinically relevant stimulation. Clinical DBS devices typically apply high-frequency voltage-controlled stimulation, and as a result, the injected current is directly regulated by the impedance of the electrode-tissue interface. We monitored the impedance of scaled-down clinical DBS electrodes implanted in the thalamus and subthalamic nucleus of a rhesus macaque using electrode impedance spectroscopy (EIS) measurements ranging from 0.5 Hz to 10 kHz. To further characterize our measurements, equivalent circuit models of the electrode-tissue interface were used to quantify the role of various interface components in producing the observed electrode impedance. Following implantation, the DBS electrode impedance increased and a semicircular arc was observed in the high-frequency range of the EIS measurements, commonly referred to as the tissue component of the impedance. Clinically relevant stimulation produced a rapid decrease in electrode impedance with extensive changes in the tissue component. These post-operative and stimulation-induced changes in impedance could play an important role in the observed functional effects of voltage-controlled DBS and should be considered during clinical stimulation parameter selection and chronic animal research studies.

  15. Probabilistic Analysis of Activation Volumes Generated During Deep Brain Stimulation

    PubMed Central

    Butson, Christopher R.; Cooper, Scott E.; Henderson, Jaimie M.; Wolgamuth, Barbara; McIntyre, Cameron C.

    2010-01-01

    Deep brain stimulation (DBS) is an established therapy for the treatment of Parkinson’s disease (PD) and shows great promise for the treatment of several other disorders. However, while the clinical analysis of DBS has received great attention, a relative paucity of quantitative techniques exists to define the optimal surgical target and most effective stimulation protocol for a given disorder. In this study we describe a methodology that represents an evolutionary addition to the concept of a probabilistic brain atlas, which we call a probabilistic stimulation atlas (PSA). We outline steps to combine quantitative clinical outcome measures with advanced computational models of DBS to identify regions where stimulation-induced activation could provide the best therapeutic improvement on a per-symptom basis. While this methodology is relevant to any form of DBS, we present example results from subthalamic nucleus (STN) DBS for PD. We constructed patient-specific computer models of the volume of tissue activated (VTA) for 163 different stimulation parameter settings which were tested in six patients. We then assigned clinical outcome scores to each VTA and compiled all of the VTAs into a PSA to identify stimulation-induced activation targets that maximized therapeutic response with minimal side effects. The results suggest that selection of both electrode placement and clinical stimulation parameter settings could be tailored to the patient’s primary symptoms using patient-specific models and PSAs. PMID:20974269

  16. A PC-based system for predicting movement from deep brain signals in Parkinson's disease.

    PubMed

    Loukas, Constantinos; Brown, Peter

    2012-07-01

    There is much current interest in deep brain stimulation (DBS) of the subthalamic nucleus (STN) for the treatment of Parkinson's disease (PD). This type of surgery has enabled unprecedented access to deep brain signals in the awake human. In this paper we present an easy-to-use computer based system for recording, displaying, archiving, and processing electrophysiological signals from the STN. The system was developed for predicting self-paced hand-movements in real-time via the online processing of the electrophysiological activity of the STN. It is hoped that such a computerised system might have clinical and experimental applications. For example, those sites within the STN most relevant to the processing of voluntary movement could be identified through the predictive value of their activities with respect to the timing of future movement.

  17. Deep brain stimulation for Parkinson's disease prior to L-dopa treatment: A case report

    PubMed Central

    Servello, Domenico; Saleh, Christian; Bona, Alberto R.; Zekaj, Edvin; Zanaboni, Carlotta; Porta, Mauro

    2016-01-01

    Background: Leva-dopa (L-dopa) is the gold-standard treatment for Parkinson's disease (PD). Deep brain stimulation is generally reserved for patients who become refractory to l-dopa treatment. Case Description: We present a male patient with a 9-year course of PD who at 53 years of age preferred deep brain stimulation (DBS) of the subthalamic nucleus over initial l-dopa treatment. The patient argued that he wanted to avoid the serious adverse effects of l-dopa, which would have presented within his time of full professional activity. DBS resulted in significant motor improvement lasting for 6 years without l-dopa treatment. Conclusion: Large multicentre-based international trials with long follow-ups are needed to answer the effectiveness of early DBS in PD. PMID:27990314

  18. Effects of Stimulation of the Subthalamic Nucleus on Naming and Reading Nouns and Verbs in Parkinson's Disease

    ERIC Educational Resources Information Center

    Silveri, Maria Caterina; Ciccarelli, Nicoletta; Baldonero, Eleonora; Piano, Carla; Zinno, Massimiliano; Soleti, Francesco; Bentivoglio, Anna Rita; Albanese, Alberto; Daniele, Antonio

    2012-01-01

    An impairment for verbs has been described in patients with Parkinson's disease (PD), suggesting that a disruption of frontal-subcortical circuits may result in dysfunction of the neural systems involved in action-verb processing. A previous study suggested that deep brain stimulation (DBS) of the subthalamic nucleus (STN) during verb generation…

  19. Effects of Stimulation of the Subthalamic Nucleus on Naming and Reading Nouns and Verbs in Parkinson's Disease

    ERIC Educational Resources Information Center

    Silveri, Maria Caterina; Ciccarelli, Nicoletta; Baldonero, Eleonora; Piano, Carla; Zinno, Massimiliano; Soleti, Francesco; Bentivoglio, Anna Rita; Albanese, Alberto; Daniele, Antonio

    2012-01-01

    An impairment for verbs has been described in patients with Parkinson's disease (PD), suggesting that a disruption of frontal-subcortical circuits may result in dysfunction of the neural systems involved in action-verb processing. A previous study suggested that deep brain stimulation (DBS) of the subthalamic nucleus (STN) during verb generation…

  20. Accurate CT-MR image registration for deep brain stimulation: a multi-observer evaluation study

    NASA Astrophysics Data System (ADS)

    Rühaak, Jan; Derksen, Alexander; Heldmann, Stefan; Hallmann, Marc; Meine, Hans

    2015-03-01

    Since the first clinical interventions in the late 1980s, Deep Brain Stimulation (DBS) of the subthalamic nucleus has evolved into a very effective treatment option for patients with severe Parkinson's disease. DBS entails the implantation of an electrode that performs high frequency stimulations to a target area deep inside the brain. A very accurate placement of the electrode is a prerequisite for positive therapy outcome. The assessment of the intervention result is of central importance in DBS treatment and involves the registration of pre- and postinterventional scans. In this paper, we present an image processing pipeline for highly accurate registration of postoperative CT to preoperative MR. Our method consists of two steps: a fully automatic pre-alignment using a detection of the skull tip in the CT based on fuzzy connectedness, and an intensity-based rigid registration. The registration uses the Normalized Gradient Fields distance measure in a multilevel Gauss-Newton optimization framework and focuses on a region around the subthalamic nucleus in the MR. The accuracy of our method was extensively evaluated on 20 DBS datasets from clinical routine and compared with manual expert registrations. For each dataset, three independent registrations were available, thus allowing to relate algorithmic with expert performance. Our method achieved an average registration error of 0.95mm in the target region around the subthalamic nucleus as compared to an inter-observer variability of 1.12 mm. Together with the short registration time of about five seconds on average, our method forms a very attractive package that can be considered ready for clinical use.

  1. Weight Gain following Pallidal Deep Brain Stimulation: A PET Study

    PubMed Central

    Sauleau, Paul; Drapier, Sophie; Duprez, Joan; Houvenaghel, Jean-François; Dondaine, Thibaut; Haegelen, Claire; Drapier, Dominique; Jannin, Pierre; Robert, Gabriel; Le Jeune, Florence; Vérin, Marc

    2016-01-01

    The mechanisms behind weight gain following deep brain stimulation (DBS) surgery seem to be multifactorial and suspected depending on the target, either the subthalamic nucleus (STN) or the globus pallidus internus (GPi). Decreased energy expenditure following motor improvement and behavioral and/or metabolic changes are possible explanations. Focusing on GPi target, our objective was to analyze correlations between changes in brain metabolism (measured with PET) and weight gain following GPi-DBS in patients with Parkinson’s disease (PD). Body mass index was calculated and brain activity prospectively measured using 2-deoxy-2[18F]fluoro-D-glucose PET four months before and four months after the start of GPi-DBS in 19 PD patients. Dopaminergic medication was included in the analysis to control for its possible influence on brain metabolism. Body mass index increased significantly by 0.66 ± 1.3 kg/m2 (p = 0.040). There were correlations between weight gain and changes in brain metabolism in premotor areas, including the left and right superior gyri (Brodmann area, BA 6), left superior gyrus (BA 8), the dorsolateral prefrontal cortex (right middle gyrus, BAs 9 and 46), and the left and right somatosensory association cortices (BA 7). However, we found no correlation between weight gain and metabolic changes in limbic and associative areas. Additionally, there was a trend toward a correlation between reduced dyskinesia and weight gain (r = 0.428, p = 0.067). These findings suggest that, unlike STN-DBS, motor improvement is the major contributing factor for weight gain following GPi-DBS PD, confirming the motor selectivity of this target. PMID:27070317

  2. Weight Gain following Pallidal Deep Brain Stimulation: A PET Study.

    PubMed

    Sauleau, Paul; Drapier, Sophie; Duprez, Joan; Houvenaghel, Jean-François; Dondaine, Thibaut; Haegelen, Claire; Drapier, Dominique; Jannin, Pierre; Robert, Gabriel; Le Jeune, Florence; Vérin, Marc

    2016-01-01

    The mechanisms behind weight gain following deep brain stimulation (DBS) surgery seem to be multifactorial and suspected depending on the target, either the subthalamic nucleus (STN) or the globus pallidus internus (GPi). Decreased energy expenditure following motor improvement and behavioral and/or metabolic changes are possible explanations. Focusing on GPi target, our objective was to analyze correlations between changes in brain metabolism (measured with PET) and weight gain following GPi-DBS in patients with Parkinson's disease (PD). Body mass index was calculated and brain activity prospectively measured using 2-deoxy-2[18F]fluoro-D-glucose PET four months before and four months after the start of GPi-DBS in 19 PD patients. Dopaminergic medication was included in the analysis to control for its possible influence on brain metabolism. Body mass index increased significantly by 0.66 ± 1.3 kg/m2 (p = 0.040). There were correlations between weight gain and changes in brain metabolism in premotor areas, including the left and right superior gyri (Brodmann area, BA 6), left superior gyrus (BA 8), the dorsolateral prefrontal cortex (right middle gyrus, BAs 9 and 46), and the left and right somatosensory association cortices (BA 7). However, we found no correlation between weight gain and metabolic changes in limbic and associative areas. Additionally, there was a trend toward a correlation between reduced dyskinesia and weight gain (r = 0.428, p = 0.067). These findings suggest that, unlike STN-DBS, motor improvement is the major contributing factor for weight gain following GPi-DBS PD, confirming the motor selectivity of this target.

  3. Deep Brain Stimulation May Ease Tourette 'Tics'

    MedlinePlus

    ... https://medlineplus.gov/news/fullstory_164573.html Deep Brain Stimulation May Ease Tourette 'Tics' But neurology experts ... may benefit from having electrodes implanted in the brain, a small study suggests. The procedure, known as ...

  4. Deep Brain Stimulation for Obesity

    PubMed Central

    Sussman, Eric S; Zhang, Michael; Pendharkar, Arjun V; Azagury, Dan E; Bohon, Cara; Halpern, Casey H

    2015-01-01

    Obesity is now the third leading cause of preventable death in the US, accounting for 216,000 deaths annually and nearly 100 billion dollars in health care costs. Despite advancements in bariatric surgery, substantial weight regain and recurrence of the associated metabolic syndrome still occurs in almost 20-35% of patients over the long-term, necessitating the development of novel therapies. Our continually expanding knowledge of the neuroanatomic and neuropsychiatric underpinnings of obesity has led to increased interest in neuromodulation as a new treatment for obesity refractory to current medical, behavioral, and surgical therapies. Recent clinical trials of deep brain stimulation (DBS) in chronic cluster headache, Alzheimer’s disease, and depression and obsessive-compulsive disorder have demonstrated the safety and efficacy of targeting the hypothalamus and reward circuitry of the brain with electrical stimulation, and thus provide the basis for a neuromodulatory approach to treatment-refractory obesity. In this study, we review the literature implicating these targets for DBS in the neural circuitry of obesity. We will also briefly review ethical considerations for such an intervention, and discuss genetic secondary-obesity syndromes that may also benefit from DBS. In short, we hope to provide the scientific foundation to justify trials of DBS for the treatment of obesity targeting these specific regions of the brain. PMID:26180683

  5. Introduction to Deep Brain Stimulation.

    PubMed

    Lozano, Andres M; Gross, Robert E

    2017-04-01

    It is estimated that over 160,000 patients worldwide have received deep brain stimulation (DBS) to date predominantly for Parkinson's disease and other movement disorders. With the success of this therapy, a greater appreciation of the clinical benefits and adverse effects is being realized. Neurosurgeons are increasingly paying attention to the technical details of these procedures and optimizing targeting, surgical techniques, and programming to improve outcomes. In this issue, the nuances of surgical techniques for DBS are covered by Dr. House. Dr. Toda et al. and Mr. Chartrain et al. tackle the approach to treating tremors, either essential tremor or Holmes tremor, using either a single target or, in cases of difficult-to-treat tremors, using more than one target and interleaving the stimulation. These abstracts and videos will be appreciated by both those who are being initiated to DBS and the more seasoned practitioners who are looking for helpful hints to tackle challenging cases.

  6. Mechanisms of deep brain stimulation

    PubMed Central

    Cheng, Jennifer J.; Eskandar, Emad N.

    2015-01-01

    Deep brain stimulation (DBS) is widely used for the treatment of movement disorders including Parkinson's disease, essential tremor, and dystonia and, to a lesser extent, certain treatment-resistant neuropsychiatric disorders including obsessive-compulsive disorder. Rather than a single unifying mechanism, DBS likely acts via several, nonexclusive mechanisms including local and network-wide electrical and neurochemical effects of stimulation, modulation of oscillatory activity, synaptic plasticity, and, potentially, neuroprotection and neurogenesis. These different mechanisms vary in importance depending on the condition being treated and the target being stimulated. Here we review each of these in turn and illustrate how an understanding of these mechanisms is inspiring next-generation approaches to DBS. PMID:26510756

  7. Deep brain stimulation: postoperative issues.

    PubMed

    Deuschl, Günther; Herzog, Jan; Kleiner-Fisman, Galit; Kubu, Cynthia; Lozano, Andres M; Lyons, Kelly E; Rodriguez-Oroz, Maria C; Tamma, Filippo; Tröster, Alexander I; Vitek, Jerrold L; Volkmann, Jens; Voon, Valerie

    2006-06-01

    Numerous factors need to be taken into account when managing a patient with Parkinson's disease (PD) after deep brain stimulation (DBS). Questions such as when to begin programming, how to conduct a programming screen, how to assess the effects of programming, and how to titrate stimulation and medication for each of the targeted sites need to be addressed. Follow-up care should be determined, including patient adjustments of stimulation, timing of follow-up visits and telephone contact with the patient, and stimulation and medication conditions during the follow-up assessments. A management plan for problems that can arise after DBS such as weight gain, dyskinesia, axial symptoms, speech dysfunction, muscle contractions, paresthesia, eyelid, ocular and visual disturbances, and behavioral and cognitive problems should be developed. Long-term complications such as infection or erosion, loss of effect, intermittent stimulation, tolerance, and pain or discomfort can develop and need to be managed. Other factors that need consideration are social and job-related factors, development of dementia, general medical issues, and lifestyle changes. This report from the Consensus on Deep Brain Stimulation for Parkinson's Disease, a project commissioned by the Congress of Neurological Surgeons and the Movement Disorder Society, outlines answers to a series of questions developed to address all aspects of DBS postoperative management and decision-making with a systematic overview of the literature (until mid-2004) and by the expert opinion of the authors. The report has been endorsed by the Scientific Issues Committee of the Movement Disorder Society and the American Society of Stereotactic and Functional Neurosurgery.

  8. Orientation selective deep brain stimulation

    NASA Astrophysics Data System (ADS)

    Lehto, Lauri J.; Slopsema, Julia P.; Johnson, Matthew D.; Shatillo, Artem; Teplitzky, Benjamin A.; Utecht, Lynn; Adriany, Gregor; Mangia, Silvia; Sierra, Alejandra; Low, Walter C.; Gröhn, Olli; Michaeli, Shalom

    2017-02-01

    Objective. Target selectivity of deep brain stimulation (DBS) therapy is critical, as the precise locus and pattern of the stimulation dictates the degree to which desired treatment responses are achieved and adverse side effects are avoided. There is a clear clinical need to improve DBS technology beyond currently available stimulation steering and shaping approaches. We introduce orientation selective neural stimulation as a concept to increase the specificity of target selection in DBS. Approach. This concept, which involves orienting the electric field along an axonal pathway, was tested in the corpus callosum of the rat brain by freely controlling the direction of the electric field on a plane using a three-electrode bundle, and monitoring the response of the neurons using functional magnetic resonance imaging (fMRI). Computational models were developed to further analyze axonal excitability for varied electric field orientation. Main results. Our results demonstrated that the strongest fMRI response was observed when the electric field was oriented parallel to the axons, while almost no response was detected with the perpendicular orientation of the electric field relative to the primary fiber tract. These results were confirmed by computational models of the experimental paradigm quantifying the activation of radially distributed axons while varying the primary direction of the electric field. Significance. The described strategies identify a new course for selective neuromodulation paradigms in DBS based on axonal fiber orientation.

  9. The impact of deep brain stimulation on tinnitus

    PubMed Central

    Smit, Jasper V.; Janssen, Marcus L. F.; Engelhard, Malou; de Bie, Rob M. A.; Schuurman, P. Richard; Contarino, Maria F.; Mosch, Arne; Temel, Yasin; Stokroos, Robert J.

    2016-01-01

    Background: Tinnitus is a disorder of the nervous system that cannot be adequately treated with current therapies. The effect of neuromodulation induced by deep brain stimulation (DBS) on tinnitus has not been studied well. This study investigated the effect of DBS on tinnitus by use of a multicenter questionnaire study. Methods: Tinnitus was retrospectively assessed prior to DBS and at the current situation (with DBS). From the 685 questionnaires, 443 were returned. A control group was one-to-one matched to DBS patients who had tinnitus before DBS (n = 61). Tinnitus was assessed by the tinnitus handicap inventory (THI) and visual analog scales (VAS) of loudness and burden. Results: The THI decreased significantly during DBS compared to the situation prior to surgery (from 18.9 to 15.1, P < .001), which was only significant for DBS in the subthalamic nucleus (STN). The THI in the control group (36.9 to 35.5, P = 0.50) and other DBS targets did not change. The VAS loudness increased in the control group (5.4 to 6.0 P < .01). Conclusion: DBS might have a modulatory effect on tinnitus. Our study suggests that DBS of the STN may have a beneficial effect on tinnitus, but most likely other nuclei linked to the tinnitus circuitry might be even more effective. PMID:27994936

  10. Weight change following deep brain stimulation for movement disorders.

    PubMed

    Strowd, Roy E; Cartwright, Michael S; Passmore, Leah V; Ellis, Thomas L; Tatter, Stephen B; Siddiqui, Mustafa S

    2010-08-01

    Patients with Parkinson's disease (PD) and essential tremor (ET) tend to lose weight progressively over years. Weight gain following deep brain stimulation (DBS) of the subthalamic nucleus (STN) for treatment of PD has been documented in several studies that were limited by small sample size and exclusive focus on PD patients with STN stimulation. The current study was undertaken to examine weight change in a large sample of movement disorder patients following DBS. A retrospective review was undertaken of 182 patient charts following DBS of the STN, ventralis intermedius nucleus of the thalamus (VIM), and globus pallidus internus (GPi). Weight was collected preoperatively and postoperatively up to 24 months following surgery. Data were adjusted for baseline weight and multivariate linear regression was performed with repeated measures to assess weight change. Statistically significant mean weight gain of 1.8 kg (2.8% increase from baseline, p = 0.0113) was observed at a rate of approximately 1 kg per year up to 24 months following surgery. This gain was not predicted by age, gender, diagnosis, or stimulation target in a multivariate model. Significant mean weight gain of 2.3 kg (p = 0.0124) or 4.2% was observed in our PD patients. Most patients with PD and ET gain weight following DBS, and this gain is not predicted by age, gender, diagnosis, or stimulation target.

  11. Intracerebral abscess: a rare complication of Deep Brain Stimulation.

    PubMed

    Brandão, Eva; Rosas, Maria José; Abreu, Pedro; Linhares, Paulo; Vaz, Rui

    2013-01-01

    Deep Brain Stimulation (DBS) is a therapeutic option for some forms of Parkinson's disease (PD). The main adverse effects of this surgery are: infection (2-9%), haemorrhage (1-4%) and seizures (1-3%). We report a rare complication of DBS: an intracranial abscess. A 59-year-old male who had suffered PD for 19 years was submitted to bilateral subthalamic nucleus DBS in September 2003, when he was 52. One month later, he developed an inflammatory reaction of the skin and subcutaneous tissue surrounding the area of the subcutaneous DBS system. No infectious agent was isolated. In the following 12 months he required 5 major surgeries due to a process of systematic inflammation/infection throughout different locations of the DBS system. A few days after removal of the DBS device, he developed a right oculomotor nerve paresis and mild left hemiparesis. A CT scan revealed an abscess in the right thalamo-mesencephalic area. Both the new neurological deficits and the previous tremor and rigidity improved after surgical drainage and medical treatment. This case report illustrates a rare complication of DBS surgery. Nevertheless, Parkinsonism improved, probably because the abscess acted like a subthalomotomy. Copyright © 2011 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

  12. Customizing deep brain stimulation to the patient using computational models.

    PubMed

    McIntyre, Cameron C; Frankenmolle, Anneke M; Wu, Jennifer; Noecker, Angela M; Alberts, Jay L

    2009-01-01

    Bilateral subthalamic (STN) deep brain stimulation (DBS) is effective in improving the cardinal motor signs of advanced Parkinson's disease (PD); however declines in cognitive function have been associated with this procedure. The aim of this study was to assess cognitive-motor performance of 10 PD patients implanted with STN DBS systems during either clinically determined stimulation settings or settings derived from a computational model. Cicerone DBS software was used to define the model parameters such that current spread to non-motor areas of the STN was minimized. Clinically determined and model defined parameters were equally effective in improving motor scores on the traditional clinical rating scale (UPDRS-III). Under modest dual-task conditions, cognitive-motor performance was worse with clinically determined compared to model derived parameters. In addition, the model parameters provided a 66% reduction in power consumption. These results indicate that the cognitive-motor declines associated with bilateral STN can be mitigated, without compromising motor benefits, utilizing stimulation parameters that minimize current spread into non-motor regions of the STN.

  13. Customizing Deep Brain Stimulation to the Patient Using Computational Models

    PubMed Central

    McIntyre, Cameron C.; Frankenmolle, Anneke; Wu, Jennifer; Noecker, Angela M.; Alberts, Jay L.

    2011-01-01

    Bilateral subthalamic (STN) deep brain stimulation (DBS) is effective in improving the cardinal motor signs of advanced Parkinson's disease (PD); however declines in cognitive function have been associated with this procedure. The aim of this study was to assess cognitive-motor performance of 10 PD patients implanted with STN DBS systems during either clinically determined stimulation settings or settings derived from a computational model. Cicerone DBS software was used to define the model parameters such that current spread to non-motor areas of the STN was minimized. Clinically determined and model defined parameters were equally effective in improving motor scores on the traditional clinical rating scale (UPDRS-III). Under modest dual-task conditions, cognitive-motor performance was worse with clinically determined compared to model derived parameters. In addition, the model parameters provided a 33% reduction in power consumption. These results indicate that the cognitivemotor declines associated with bilateral STN can be mitigated, without compromising motor benefits, utilizing stimulation parameters that minimize current spread into non-motor regions of the STN. PMID:19965023

  14. Personality Changes after Deep Brain Stimulation in Parkinson's Disease

    PubMed Central

    Pham, Uyen; Solbakk, Anne-Kristin; Skogseid, Inger-Marie; Pripp, Are Hugo; Konglund, Ane Eidahl; Andersson, Stein; Haraldsen, Ira Ronit; Aarsland, Dag; Dietrichs, Espen; Malt, Ulrik Fredrik

    2015-01-01

    Objectives. Deep brain stimulation of the subthalamic nucleus (STN-DBS) is a recognized therapy that improves motor symptoms in advanced Parkinson's disease (PD). However, little is known about its impact on personality. To address this topic, we have assessed personality traits before and after STN-DBS in PD patients. Methods. Forty patients with advanced PD were assessed with the Temperament and Character Inventory (TCI): the Urgency, Premeditation, Perseverance, Sensation Seeking impulsive behaviour scale (UPPS), and the Neuroticism and Lie subscales of the Eysenck Personality Questionnaire (EPQ-N, EPQ-L) before surgery and after three months of STN-DBS. Collateral information obtained from the UPPS was also reported. Results. Despite improvement in motor function and reduction in dopaminergic dosage patients reported lower score on the TCI Persistence and Self-Transcendence scales, after three months of STN-DBS, compared to baseline (P = 0.006; P = 0.024). Relatives reported significantly increased scores on the UPPS Lack of Premeditation scale at follow-up (P = 0.027). Conclusion. STN-DBS in PD patients is associated with personality changes in the direction of increased impulsivity. PMID:25705545

  15. Low-frequency deep brain stimulation for movement disorders.

    PubMed

    Baizabal-Carvallo, José Fidel; Alonso-Juarez, Marlene

    2016-10-01

    Traditionally, deep brain stimulation (DBS) for movement disorders (MDs) is provided using stimulation frequencies equal to or above 100 Hz. However, recent evidence suggests that relatively low-frequency stimulation (LFS) below 100 Hz is an option to treat some patients with MDs. We aimed to review the clinical and pathophysiological evidence supporting the use of stimulation frequencies below 100 Hz in different MDs. Stimulation of the subthalamic nucleus at 60 Hz has provided benefit in gait and other axial symptoms such as swallowing and speech. Stimulation of the pedunculopontine nucleus between 20 and 45 Hz can provide benefit in freezing of gait, cognition, and sleep quality in select patients with Parkinson's disease. Stimulation of the globus pallidus internus below 100 Hz in patients with dystonia has provided benefit at the beginning of the therapy, although progressively higher stimulation frequencies seem to be necessary to maintain the clinical benefit. Relative LFS can lower energy requirements and reduce battery usage-a useful feature, particularly in patients treated with high current energy. DBS at frequencies below 100 Hz is a therapeutic option in select cases of Parkinson's disease with freezing of gait and other axial symptoms, and in select patients with dystonia and other hyperkinetic movements, particularly those requiring an energy-saving strategy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Deep brain stimulation for intractable tardive dystonia: Literature overview.

    PubMed

    Sobstyl, Michał; Ząbek, Mirosław

    2016-01-01

    Tardive dystonia (TD) represents a side effect of prolonged intake of dopamine receptor blocking compounds. TD can be a disabling movement disorder persisting despite available medical treatment. Deep brain stimulation (DBS) has been reported successful in this condition although the number of treated patients with TD is still limited to small clinical studies or case reports. The aim of this study was to present the systematical overview of the existing literature regarding DBS for intractable TD. A literature search was carried out in PudMed. Clinical case series or case reports describing the patients with TD after DBS treatment were included in the present overview. Literature search revealed 19 articles reporting 59 individuals operated for TD. GPi was the target in 55 patients, while subthalamic nucleus (STN) was the target in the remaining 4. In most studies the motor part of Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) was improved by more than 80% when compared to preoperative BFMDRS scores. The performed literature analysis indicates that bilateral GPi DBS is an effective treatment for disabling TD. The response of TD to bilateral GPi DBS may be very rapid and occurs within days/weeks after the procedure. The efficacy of bilateral GPi DBS in TD patients is comparable to results achieved in patients with primary generalized dystonia. Copyright © 2016 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  17. Deep brain stimulation activation volumes and their association with neurophysiological mapping and therapeutic outcomes

    PubMed Central

    Maks, Christopher B.; Butson, Christopher R.; Walter, Benjamin L.; Vitek, Jerrold L.; McIntyre, Cameron C.

    2010-01-01

    Objective Despite the clinical success of deep brain stimulation (DBS) for the treatment of Parkinson’s disease (PD), little is known about the electrical spread of the stimulation. The primary goal of this study was to integrate neuroimaging, neurophysiology, and neurostimulation data sets from 10 PD patients, unilaterally implanted with subthalamic nucleus (STN) DBS electrodes, to identify the theoretical volume of tissue activated (VTA) by clinically defined therapeutic stimulation parameters. Methods Each patient-specific model was created with a series of five steps: 1) definition of the neurosurgical stereotactic coordinate system within the context of pre-operative imaging data; 2) entry of intra-operative microelectrode recording locations from neurophysiologically defined thalamic, subthalamic, and substantia nigra neurons into the context of the imaging data; 3) fitting a 3D brain atlas to the neuroanatomy and neurophysiology of the patient; 4) positioning the DBS electrode in the documented stereotactic location, verified by post-operative imaging data; and 5) calculation of the VTA using a diffusion tensor based finite element neurostimulation model. Results The patient-specific models show that therapeutic benefit was achieved with direct stimulation of a wide range of anatomical structures in the subthalamic region. Interestingly, of the 5 patients exhibiting a greater than 40% improvement in their unified PD rating scale (UPDRS), all but one had the majority of their VTA outside the atlas defined borders of the STN. Further, of the 5 patients with less than 40% UPDRS improvement all but one had the majority of their VTA inside the STN. Conclusions Our results are consistent with previous studies suggesting that therapeutic benefit is associated with electrode contacts near the dorsal border of the STN, and provide quantitative estimates of the electrical spread of the stimulation in a clinically relevant context. PMID:18403440

  18. Adaptive Deep Brain Stimulation In Advanced Parkinson Disease

    PubMed Central

    Little, Simon; Pogosyan, Alex; Neal, Spencer; Zavala, Baltazar; Zrinzo, Ludvic; Hariz, Marwan; Foltynie, Thomas; Limousin, Patricia; Ashkan, Keyoumars; FitzGerald, James; Green, Alexander L; Aziz, Tipu Z; Brown, Peter

    2013-01-01

    Objective: Brain–computer interfaces (BCIs) could potentially be used to interact with pathological brain signals to intervene and ameliorate their effects in disease states. Here, we provide proof-of-principle of this approach by using a BCI to interpret pathological brain activity in patients with advanced Parkinson disease (PD) and to use this feedback to control when therapeutic deep brain stimulation (DBS) is delivered. Our goal was to demonstrate that by personalizing and optimizing stimulation in real time, we could improve on both the efficacy and efficiency of conventional continuous DBS. Methods: We tested BCI-controlled adaptive DBS (aDBS) of the subthalamic nucleus in 8 PD patients. Feedback was provided by processing of the local field potentials recorded directly from the stimulation electrodes. The results were compared to no stimulation, conventional continuous stimulation (cDBS), and random intermittent stimulation. Both unblinded and blinded clinical assessments of motor effect were performed using the Unified Parkinson's Disease Rating Scale. Results: Motor scores improved by 66% (unblinded) and 50% (blinded) during aDBS, which were 29% (p = 0.03) and 27% (p = 0.005) better than cDBS, respectively. These improvements were achieved with a 56% reduction in stimulation time compared to cDBS, and a corresponding reduction in energy requirements (p < 0.001). aDBS was also more effective than no stimulation and random intermittent stimulation. Interpretation BCI-controlled DBS is tractable and can be more efficient and efficacious than conventional continuous neuromodulation for PD. Ann Neurol 2013;74:449–457 PMID:23852650

  19. Bilateral Deep Brain Stimulation vs Best Medical Therapy for Patients With Advanced Parkinson Disease

    PubMed Central

    Weaver, Frances M.; Follett, Kenneth; Stern, Matthew; Hur, Kwan; Harris, Crystal; Marks, William J.; Rothlind, Johannes; Sagher, Oren; Reda, Domenic; Moy, Claudia S.; Pahwa, Rajesh; Burchiel, Kim; Hogarth, Penelope; Lai, Eugene C.; Duda, John E.; Holloway, Kathryn; Samii, Ali; Horn, Stacy; Bronstein, Jeff; Stoner, Gatana; Heemskerk, Jill; Huang, Grant D.

    2010-01-01

    Context Deep brain stimulation is an accepted treatment for advanced Parkinson disease (PD), although there are few randomized trials comparing treatments, and most studies exclude older patients. Objective To compare 6-month outcomes for patients with PD who received deep brain stimulation or best medical therapy. Design, Setting, and Patients Randomized controlled trial of patients who received either deep brain stimulation or best medical therapy, stratified by study site and patient age (<70 years vs ≥70 years) at 7 Veterans Affairs and 6 university hospitals between May 2002 and October 2005. A total of 255 patients with PD (Hoehn and Yahr stage ≥2 while not taking medications) were enrolled; 25% were aged 70 years or older. The final 6-month follow-up visit occurred in May 2006. Intervention Bilateral deep brain stimulation of the subthalamic nucleus (n=60) or globus pallidus (n=61). Patients receiving best medical therapy (n=134) were actively managed by movement disorder neurologists. Main Outcome Measures The primary outcome was time spent in the “on” state (good motor control with unimpeded motor function) without troubling dyskinesia, using motor diaries. Other outcomes included motor function, quality of life, neurocognitive function, and adverse events. Results Patients who received deep brain stimulation gained a mean of 4.6 h/d of on time without troubling dyskinesia compared with 0 h/d for patients who received best medical therapy (between group mean difference, 4.5 h/d [95% CI, 3.7-5.4 h/d]; P<.001). Motor function improved significantly (P<.001) with deep brain stimulation vs best medical therapy, such that 71% of deep brain stimulation patients and 32% of best medical therapy patients experienced clinically meaningful motor function improvements (≥5 points). Compared with the best medical therapy group, the deep brain stimulation group experienced significant improvements in the summary measure of quality of life and on 7 of 8 PD

  20. Distinct roles of dopamine and subthalamic nucleus in learning and probabilistic decision making

    PubMed Central

    Bogacz, Rafal; Javed, Shazia; Mooney, Lucy K.; Murphy, Gillian; Keeley, Sophie; Whone, Alan L.

    2012-01-01

    Even simple behaviour requires us to make decisions based on combining multiple pieces of learned and new information. Making such decisions requires both learning the optimal response to each given stimulus as well as combining probabilistic information from multiple stimuli before selecting a response. Computational theories of decision making predict that learning individual stimulus–response associations and rapid combination of information from multiple stimuli are dependent on different components of basal ganglia circuitry. In particular, learning and retention of memory, required for optimal response choice, are significantly reliant on dopamine, whereas integrating information probabilistically is critically dependent upon functioning of the glutamatergic subthalamic nucleus (computing the ‘normalization term’ in Bayes’ theorem). Here, we test these theories by investigating 22 patients with Parkinson’s disease either treated with deep brain stimulation to the subthalamic nucleus and dopaminergic therapy or managed with dopaminergic therapy alone. We use computerized tasks that probe three cognitive functions—information acquisition (learning), memory over a delay and information integration when multiple pieces of sequentially presented information have to be combined. Patients performed the tasks ON or OFF deep brain stimulation and/or ON or OFF dopaminergic therapy. Consistent with the computational theories, we show that stopping dopaminergic therapy impairs memory for probabilistic information over a delay, whereas deep brain stimulation to the region of the subthalamic nucleus disrupts decision making when multiple pieces of acquired information must be combined. Furthermore, we found that when participants needed to update their decision on the basis of the last piece of information presented in the decision-making task, patients with deep brain stimulation of the subthalamic nucleus region did not slow down appropriately to revise their

  1. Distinct roles of dopamine and subthalamic nucleus in learning and probabilistic decision making.

    PubMed

    Coulthard, Elizabeth J; Bogacz, Rafal; Javed, Shazia; Mooney, Lucy K; Murphy, Gillian; Keeley, Sophie; Whone, Alan L

    2012-12-01

    Even simple behaviour requires us to make decisions based on combining multiple pieces of learned and new information. Making such decisions requires both learning the optimal response to each given stimulus as well as combining probabilistic information from multiple stimuli before selecting a response. Computational theories of decision making predict that learning individual stimulus-response associations and rapid combination of information from multiple stimuli are dependent on different components of basal ganglia circuitry. In particular, learning and retention of memory, required for optimal response choice, are significantly reliant on dopamine, whereas integrating information probabilistically is critically dependent upon functioning of the glutamatergic subthalamic nucleus (computing the 'normalization term' in Bayes' theorem). Here, we test these theories by investigating 22 patients with Parkinson's disease either treated with deep brain stimulation to the subthalamic nucleus and dopaminergic therapy or managed with dopaminergic therapy alone. We use computerized tasks that probe three cognitive functions-information acquisition (learning), memory over a delay and information integration when multiple pieces of sequentially presented information have to be combined. Patients performed the tasks ON or OFF deep brain stimulation and/or ON or OFF dopaminergic therapy. Consistent with the computational theories, we show that stopping dopaminergic therapy impairs memory for probabilistic information over a delay, whereas deep brain stimulation to the region of the subthalamic nucleus disrupts decision making when multiple pieces of acquired information must be combined. Furthermore, we found that when participants needed to update their decision on the basis of the last piece of information presented in the decision-making task, patients with deep brain stimulation of the subthalamic nucleus region did not slow down appropriately to revise their plan, a

  2. Localisation of the subthalamic nucleus using Radionics Image Fusion and Stereoplan combined with field potential recording. A technical note.

    PubMed

    Liu, X; Rowe, J; Nandi, D; Hayward, G; Parkin, S; Stein, J; Aziz, T

    2001-01-01

    Subthalamic nucleus stimulation is an effective therapy for alleviating parkinsonian tremor, rigidity and bradykinesia. Although microelectrode recording is said to be essential for accurate targeting, this often prolongs the operation and the multiple recording tracts required may increase the incidence of complications, particularly haemorrhage. We describe a technique for implantation of deep brain electrodes in the subthalamic nucleus using MRI/CT fusion for anatomical localisation followed by bipolar recording of focal field potentials via the implanted stimulating electrode for neurophysiological confirmation of the stimulation site. The technique is effective, safe and requires much less time, and can be used as an alternative method to microelectrode recording. Copyright 2002 S. Karger AG, Basel

  3. Deep brain stimulation for dystonia.

    PubMed

    Vidailhet, Marie; Jutras, Marie-France; Grabli, David; Roze, Emmanuel

    2013-09-01

    The few controlled studies that have been carried out have shown that bilateral internal globus pallidum stimulation is a safe and long-term effective treatment for hyperkinetic disorders. However, most recent published data on deep brain stimulation (DBS) for dystonia, applied to different targets and patients, are still mainly from uncontrolled case reports (especially for secondary dystonia). This precludes clear determination of the efficacy of this procedure and the choice of the 'good' target for the 'good' patient. We performed a literature analysis on DBS for dystonia according to the expected outcome. We separated those with good evidence of favourable outcome from those with less predictable outcome. In the former group, we review the main results for primary dystonia (generalised/focal) and highlight recent data on myoclonus-dystonia and tardive dystonia (as they share, with primary dystonia, a marked beneficial effect from pallidal stimulation with good risk/benefit ratio). In the latter group, poor or variable results have been obtained for secondary dystonia (with a focus on heredodegenerative and metabolic disorders). From this overview, the main results and limits for each subgroup of patients that may help in the selection of dystonic patients who will benefit from DBS are discussed.

  4. [Deep brain stimulation and neuroethics].

    PubMed

    Katayama, Yoichi; Fukaya, Chikashi

    2009-01-01

    The use of deep brain stimulation (DBS) for mental disorders has been discussed in Japan from the viewpoint of ethical problems. Trials of experimental therapies require a basis of sound scientific rationale. New standard therapy emerges from such trials through detailed analysis of the outcome and side effects. Long-suffering patients with intractable symptoms may desperately seek an experimental therapy even though it has not yet been accepted as standard therapy. The ethical committee of each institution evaluates the level of scientific rationale and the expected level of benefits on the bias of the reported data, and decides whether the patients can receive the experimental therapy. However, the use of DBS for mental disorders is not based on sound scientific rational, since the disease mechanisms involved are far from understood. The data reported from the previous trials are insufficient for assuring the satisfactory results for mental disoder patients. Most institutions in Japan do not accept such levels of scientific rationale and expected benefits. Furthermore, from the cultural perspective, strong skepticism exists in Japan with regard to surgical interventions for mental disorders. Such an attitude is unexpectedly in harmony with many of the subjects currently discussed in the field of neuroethics. For example, who has the right to control DBS? How does someone decide the level of control of mental function by DBS? These questions are related to the discussion on how human society is formed and how the ethics are decided by considering both scientific rationale and human society.

  5. Deep brain stimulation: how does it work?

    PubMed

    Vitek, Jerrold L

    2008-03-01

    Deep brain stimulation has significantly improved the motor symptoms in patients with Parkinson's disease (PD) and other movement disorders. The mechanisms responsible for these improvements continue to be explored. Inhibition at the site of stimulation has been the prevailing explanation for the symptom improvement observed with deep brain stimulation. Research using microelectrode recording during deep brain stimulation in the MPTP monkey model of PD has helped clarify how electrical stimulation of structures within the basal ganglia-thalamocortical circuit improves motor symptoms, and suggests that activation of output and the resultant change in pattern of neuronal activity that permeates throughout the basal ganglia motor circuit is the mechanism responsible for symptom improvement.

  6. Progressive gait ataxia following deep brain stimulation for essential tremor: adverse effect or lack of efficacy?

    PubMed

    Reich, Martin M; Brumberg, Joachim; Pozzi, Nicolò G; Marotta, Giorgio; Roothans, Jonas; Åström, Mattias; Musacchio, Thomas; Lopiano, Leonardo; Lanotte, Michele; Lehrke, Ralph; Buck, Andreas K; Volkmann, Jens; Isaias, Ioannis U

    2016-09-21

    Thalamic deep brain stimulation is a mainstay treatment for severe and drug-refractory essential tremor, but postoperative management may be complicated in some patients by a progressive cerebellar syndrome including gait ataxia, dysmetria, worsening of intention tremor and dysarthria. Typically, this syndrome manifests several months after an initially effective therapy and necessitates frequent adjustments in stimulation parameters. There is an ongoing debate as to whether progressive ataxia reflects a delayed therapeutic failure due to disease progression or an adverse effect related to repeated increases of stimulation intensity. In this study we used a multimodal approach comparing clinical stimulation responses, modelling of volume of tissue activated and metabolic brain maps in essential tremor patients with and without progressive ataxia to disentangle a disease-related from a stimulation-induced aetiology. Ten subjects with stable and effective bilateral thalamic stimulation were stratified according to the presence (five subjects) of severe chronic-progressive gait ataxia. We quantified stimulated brain areas and identified the stimulation-induced brain metabolic changes by multiple (18)F-fluorodeoxyglucose positron emission tomography performed with and without active neurostimulation. Three days after deactivating thalamic stimulation and following an initial rebound of symptom severity, gait ataxia had dramatically improved in all affected patients, while tremor had worsened to the presurgical severity, thus indicating a stimulation rather than disease-related phenomenon. Models of the volume of tissue activated revealed a more ventrocaudal stimulation in the (sub)thalamic area of patients with progressive gait ataxia. Metabolic maps of both patient groups differed by an increased glucose uptake in the cerebellar nodule of patients with gait ataxia. Our data suggest that chronic progressive gait ataxia in essential tremor is a reversible cerebellar

  7. Deep brain stimulation for treatment-refractory obsessive compulsive disorder: a systematic review.

    PubMed

    Kohl, Sina; Schönherr, Deva M; Luigjes, Judy; Denys, Damiaan; Mueller, Ulf J; Lenartz, Doris; Visser-Vandewalle, Veerle; Kuhn, Jens

    2014-08-02

    Obsessive-compulsive disorder is one of the most disabling of all psychiatric illnesses. Despite available pharmacological and psychotherapeutic treatments about 10% of patients remain severely affected and are considered treatment-refractory. For some of these patients deep brain stimulation offers an appropriate treatment method. The scope of this article is to review the published data and to compare different target structures and their effectiveness. PubMed search, last update June 2013, was conducted using the terms "deep brain stimulation" and "obsessive compulsive disorder". In total 25 studies were found that reported five deep brain stimulation target structures to treat obsessive-compulsive disorder: the anterior limb of the internal capsule (five studies including 14 patients), nucleus accumbens (eight studies including 37 patients), ventral capsule/ventral striatum (four studies including 29 patients), subthalamic nucleus (five studies including 23 patients) and inferior thalamic peduncle (two studies including 6 patients). Despite the anatomical diversity, deep brain stimulation treatment results in similar response rates for the first four target structures. Inferior thalamic peduncle deep brain stimulation results in higher response rates but these results have to be interpreted with caution due to a very small number of cases. Procedure and device related adverse events are relatively low, as well as stimulation or therapy related side effects. Most stimulation related side effects are transient and decline after stimulation parameters have been changed. Deep brain stimulation in treatment-refractory obsessive-compulsive disorder seems to be a relatively safe and promising treatment option. However, based on these studies no superior target structure could be identified. More research is needed to better understand mechanisms of action and response predictors that may help to develop a more personalized approach for these severely affected

  8. Hypersexuality following subthalamic nucleus stimulation for Parkinson's disease.

    PubMed

    Doshi, Paresh; Bhargava, Pranshu

    2008-01-01

    Subthalamic nucleus (STN) stimulation is an established surgical treatment for Parkinson's disease (PD). Though the motor benefits of STN stimulation are well understood, its cognitive and behavioral effects are still not fully understood. Manic psychosis, hypersexuality, pathological gambling and mood swings are associated with advanced PD. There have been reports to suggest improvement or worsening in these symptoms following STN deep brain stimulation (DBS). We report two cases as the sole behavioral side-effects of STN stimulation despite good clinical improvement on long-term follow-up. These patients and literature review suggests the complex role of STN stimulation in motor and behavioral control.

  9. Effects of dopaminergic and subthalamic stimulation on musical performance.

    PubMed

    van Vugt, Floris T; Schüpbach, Michael; Altenmüller, Eckart; Bardinet, Eric; Yelnik, Jérôme; Hälbig, Thomas D

    2013-05-01

    Although subthalamic-deep brain stimulation (STN-DBS) is an efficient treatment for Parkinson's disease (PD), its effects on fine motor functions are not clear. We present the case of a professional violinist with PD treated with STN-DBS. DBS improved musical articulation, intonation and emotional expression and worsened timing relative to a timekeeper (metronome). The same effects were found for dopaminergic treatment. These results suggest that STN-DBS, mimicking the effects of dopaminergic stimulation, improves fine-tuned motor behaviour whilst impairing timing precision.

  10. Neuropsychological outcomes from constant current deep brain stimulation for Parkinson's disease

    PubMed Central

    Jankovic, Joseph; Tagliati, Michele; Peichel, DeLea; Okun, Michael S.

    2016-01-01

    ABSTRACT Objective The aim of this study was to evaluate the neurobehavioral safety of constant‐current subthalamic deep brain stimulation and to compare the neuropsychological effects of stimulation versus electrode placement alone. Methods A total of 136 patients with Parkinson's disease underwent bilateral subthalamic device implantation in this randomized trial. Patients received stimulation either immediately after device implantation (n = 101; active stimulation) or beginning 3 months after surgery (n = 35; delayed activation control). Patients were administered neuropsychological tests before, 3, and 12 months after device implantation. Results Neuropsychological change in stimulation and control groups were comparable. Within‐group analyses revealed declines in category and switching verbal fluency in both groups, but only the stimulation group had letter verbal fluency and Stroop task declines. Depression symptom improvements occurred in both groups, but more often in the stimulation group. Letter fluency declines were associated with worse Parkinson's Disease Questionnaire Communication subscale scores. Baseline and 12‐month comparisons (in the combined group) revealed gains in verbal and visual delayed recall scores and improvement in depression symptoms, but decrements in verbal fluency and Stroop scores. Conclusions Constant‐current bilateral subthalamic stimulation had a good cognitive safety profile except for decrements in verbal fluency and on the Stroop task. These abnormalities are related to device implantation, but stimulation likely had an additive effect. One year after surgery, the cognitive changes did not exert a detrimental effect on quality of life, although letter fluency declines were associated with communication dissatisfaction at 12 months. Improvement in depressive symptom severity appears dependent on stimulation and not placebo or lesion effects. © 2016 The Authors. Movement Disorders published by Wiley

  11. Deep brain stimulation and sleep-wake functions in Parkinson's disease: A systematic review.

    PubMed

    Eugster, Lukas; Bargiotas, Panagiotis; Bassetti, Claudio L; Michael Schuepbach, W M

    2016-11-01

    Sleep-wake disturbances (SWD) are common nonmotor symptoms (NMS) and have a great impact on quality of life of patients with Parkinson's disease (PD). Deep brain stimulation (DBS) is an established treatment in PD. While the beneficial effects of DBS on cardinal PD motor symptoms are indisputable, the data for several NMS, including sleep-wake functions, are limited and often controversial. Our primary objective was to review the literature on the impact of DBS on sleep-wake functions in patients with PD. A systematic review of articles, published in PubMed between January 1st, 2000 and December 31st, 2015 was performed to identify studies addressing the evolution of sleep-wake functions after DBS in patients with PD. Only 38 of 208 studies, involving a total of 1443 subjects, met the inclusion criteria. Most of them reported a positive effect of subthalamic DBS on sleep quality and consequently on quality of life. Seven studies used polysomnography to objectively assess sleep parameters. The data concerning subthalamic DBS and wake functions are controversial and studies using objective, laboratory-based measures for the assessment of wake functions are lacking. Very few studies assessed the impact of other DBS targets (e.g. pallidal stimulation) on SWD. Further prospective observational DBS studies assessing subjectively and objectively specific sleep-wake parameters in patients with PD are needed. Copyright © 2016. Published by Elsevier Ltd.

  12. Automatic target and trajectory identification for deep brain stimulation (DBS) procedures.

    PubMed

    Guo, Ting; Parrent, Andrew G; Peters, Terry M

    2007-01-01

    This paper presents an automatic surgical target and trajectory identification technique for planning deep brain stimulation (DBS) procedures. The probabilistic functional maps, constructed from population-based actual stimulating field information and intra-operative electrophysiological activities, were integrated into a neurosurgical visualization and navigation system to facilitate the surgical planning and guidance. In our preliminary studies, we compared the actual surgical target locations and trajectories established by an experienced stereotactic neurosurgeon with those automatically planned using our probabilistic functional maps on 10 subthalamic nucleus (STN) DBS procedures. The average displacement between the surgical target locations in both groups was 1.82mm with a standard deviation of 0.77mm. The difference between the surgical trajectories was 3.1 degrees and 2.3 degrees in the lateral-to-medial and anterior-to-posterior orientations respectively.

  13. Chronic posttraumatic movement disorder alleviated by insertion of meso-diencephalic deep brain stimulating electrode.

    PubMed

    Hooper, J; Simpson, P; Whittle, I R

    2001-10-01

    Incapacitating and drug-resistant posttraumatic movement disorders have successfully been treated by stereotactic thalamotomy. We describe the case of a young man with a posttraumatic hemiballismoid type movement disorder of the left arm, persistent for 2 years, who was selected for treatment with a thalamic deep brain stimulator. However, placement of the stimulating electrode tip at the junction of the zona incerta and subthalamic regions caused abolition of the movement disorder, and the pulse generator was not required. Reassessment over a 44-month period using multiple clinical and functional tests has confirmed continued benefit. This case adds to the reports of alleviation of movement disorders following either stereotactic thalamic mapping or placement of stimulating electrodes without macroscopic thalamic lesioning.

  14. Nonmotor outcomes in Parkinson’s disease: is deep brain stimulation better than dopamine replacement therapy?

    PubMed Central

    Kandadai, Rukmini Mridula; Jabeen, Afshan; Kannikannan, Meena A.

    2012-01-01

    Nonmotor symptoms are an integral part of Parkinson’s disease and cause significant morbidity. Pharmacological therapy helps alleviate the disease but produces nonmotor manifestations. While deep brain stimulation (DBS) has emerged as the treatment of choice for motor dysfunction, the effect on nonmotor symptoms is not well known. Compared with pharmacological therapy, bilateral subthalamic nucleus (STN)-DBS or globus pallidum interna (GPi)-DBS has significant beneficial effects on pain, sleep, gastrointestinal and urological symptoms. STN-DBS is associated with a mild worsening in verbal fluency while GPi-DBS has no effect on cognition. STN-DBS may improve cardiovascular autonomic disturbances by reducing the dose of dopaminergic drugs. Because the motor effects of STN-DBS and GPi-DBS appear to be similar, nonmotor symptoms may determine the target choice in surgery of future patients. PMID:22276074

  15. Deep Brain Stimulation in Parkinson's Disease: New and Emerging Targets for Refractory Motor and Nonmotor Symptoms

    PubMed Central

    Beecher, Grayson

    2017-01-01

    Parkinson's disease (PD) is a progressive neurodegenerative condition characterized by bradykinesia, tremor, rigidity, and postural instability (PI), in addition to numerous nonmotor manifestations. Many pharmacological therapies now exist to successfully treat PD motor symptoms; however, as the disease progresses, it often becomes challenging to treat with medications alone. Deep brain stimulation (DBS) has become a crucial player in PD treatment, particularly for patients who have disabling motor complications from medical treatment. Well-established DBS targets include the subthalamic nucleus (STN), the globus pallidus pars interna (GPi), and to a lesser degree the ventral intermediate nucleus (VIM) of the thalamus. Studies of alternative DBS targets for PD are ongoing, the majority of which have shown some clinical benefit; however, more carefully designed and controlled studies are needed. In the present review, we discuss the role of these new and emerging DBS targets in treating refractory axial motor symptoms and other motor and nonmotor symptoms (NMS). PMID:28761773

  16. Deep brain stimulation with a pre-existing cochlear implant: Surgical technique and outcome

    PubMed Central

    Eddelman, Daniel; Wewel, Joshua; Wiet, R. Mark; Metman, Leo V.; Sani, Sepehr

    2017-01-01

    Background: Patients with previously implanted cranial devices pose a special challenge in deep brain stimulation (DBS) surgery. We report the implantation of bilateral DBS leads in a patient with a cochlear implant. Technical nuances and long-term interdevice functionality are presented. Case Description: A 70-year-old patient with advancing Parkinson's disease and a previously placed cochlear implant for sensorineural hearing loss was referred for placement of bilateral DBS in the subthalamic nucleus (STN). Prior to DBS, the patient underwent surgical removal of the subgaleal cochlear magnet, followed by stereotactic MRI, frame placement, stereotactic computed tomography (CT), and merging of imaging studies. This technique allowed for successful computational merging, MRI-guided targeting, and lead implantation with acceptable accuracy. Formal testing and programming of both the devices were successful without electrical interference. Conclusion: Successful DBS implantation with high resolution MRI-guided targeting is technically feasible in patients with previously implanted cochlear implants by following proper precautions. PMID:28480109

  17. Deep brain stimulation with a pre-existing cochlear implant: Surgical technique and outcome.

    PubMed

    Eddelman, Daniel; Wewel, Joshua; Wiet, R Mark; Metman, Leo V; Sani, Sepehr

    2017-01-01

    Patients with previously implanted cranial devices pose a special challenge in deep brain stimulation (DBS) surgery. We report the implantation of bilateral DBS leads in a patient with a cochlear implant. Technical nuances and long-term interdevice functionality are presented. A 70-year-old patient with advancing Parkinson's disease and a previously placed cochlear implant for sensorineural hearing loss was referred for placement of bilateral DBS in the subthalamic nucleus (STN). Prior to DBS, the patient underwent surgical removal of the subgaleal cochlear magnet, followed by stereotactic MRI, frame placement, stereotactic computed tomography (CT), and merging of imaging studies. This technique allowed for successful computational merging, MRI-guided targeting, and lead implantation with acceptable accuracy. Formal testing and programming of both the devices were successful without electrical interference. Successful DBS implantation with high resolution MRI-guided targeting is technically feasible in patients with previously implanted cochlear implants by following proper precautions.

  18. Voice and fluency changes as a function of speech task and deep brain stimulation

    PubMed Central

    Sidtis, D.; Rogers, T.; Godier, V.; Tagliati, M.; Sidtis, J.J.

    2015-01-01

    Speaking, which naturally occurs in different modes or “tasks” such as conversation and repetition, relies on intact basal ganglia nuclei. Recent studies suggest that voice and fluency parameters are differentially affected by speech task. This study examines the effects of subcortical functionality on voice and fluency, comparing measures obtained from spontaneous and matched repeated speech samples. Parkinson subjects who are being treated with bilateral deep brain stimulation (DBS) of the subthalamic nuclei (STN) were tested with stimulators ON and OFF. Results indicated that a voice measure, harmonic to noise ratio, is improved in repetition and in DBS-ON, and that dysfluencies are more plentiful in conversation with little or variable influence of DBS condition. These findings suggest that voice and fluency are differentially affected by DBS treatment and that task conditions, interacting with subcortical functionality, influence motor speech performance. PMID:20643796

  19. Cross validation of experts versus registration methods for target localization in deep brain stimulation.

    PubMed

    Sánchez Castro, F Javier; Pollo, Claudio; Meuli, Reto; Maeder, Philippe; Cuadra, Meritxell Bach; Cuisenaire, Olivier; Villemure, Jean-Guy; Thiran, Jean-Philippe

    2005-01-01

    In the last five years, Deep Brain Stimulation (DBS) has become the most popular and effective surgical technique for the treatent of Parkinson's disease (PD). The Subthalamic Nucleus (STN) is the usual target involved when applying DBS. Unfortunately, the STN is in general not visible in common medical imaging modalities. Therefore, atlas-based segmentation is commonly considered to locate it in the images. In this paper, we propose a scheme that allows both, to perform a comparison between different registration algorithms and to evaluate their ability to locate the STN automatically. Using this scheme we can evaluate the expert variability against the error of the algorithms and we demonstrate that automatic STN location is possible and as accurate as the methods currently used.

  20. Brittle Dyskinesia Following STN but not GPi Deep Brain Stimulation

    PubMed Central

    Sriram, Ashok; Foote, Kelly D.; Oyama, Genko; Kwak, Joshua; Zeilman, Pam R.; Okun, Michael S.

    2014-01-01

    Background The aim was to describe the prevalence and characteristics of difficult to manage dyskinesia associated with subthalamic nucleus (STN) deep brain stimulation (DBS). A small subset of STN DBS patients experience troublesome dyskinesia despite optimal programming and medication adjustments. This group of patients has been referred to by some practitioners as brittle STN DBS-induced dyskinesia, drawing on comparisons with brittle diabetics experiencing severe blood sugar regulation issues and on a single description by McLellan in 1982. We sought to describe, and also to investigate how often the “brittle” phenomenon occurs in a relatively large DBS practice. Methods An Institutional Review Board-approved patient database was reviewed, and all STN and globus pallidus internus (GPi) DBS patients who had surgery at the University of Florida from July 2002 to July 2012 were extracted for analysis. Results There were 179 total STN DBS patients and, of those, four STN DBS (2.2%) cases were identified as having dyskinesia that could not be managed without the induction of an “off state,” or by the precipitation of a severe dyskinesia despite vigorous stimulation and medication adjustments. Of 75 GPi DBS cases reviewed, none (0%) was identified as having brittle dyskinesia. One STN DBS patient was successfully rescued by bilateral GPi DBS. Discussion Understanding the potential risk factors for postoperative troublesome and brittle dyskinesia may have an impact on the initial surgical target selection (STN vs. GPI) in DBS therapy. Rescue GPi DBS therapy may be a viable treatment option, though more cases will be required to verify this observation. PMID:24932426

  1. Anatomic correlates of deep brain stimulation electrode impedance.

    PubMed

    Satzer, David; Maurer, Eric W; Lanctin, David; Guan, Weihua; Abosch, Aviva

    2015-04-01

    The location of the optimal target for deep brain stimulation (DBS) of the subthalamic nucleus (STN) remains controversial. Electrode impedance affects tissue activation by DBS and has been found to vary by contact number, but no studies have examined association between impedance and anatomic location. To evaluate the relationship between electrode impedance and anatomic contact location, and to assess the clinical significance of impedance. We gathered retrospective impedance data from 101 electrodes in 73 patients with Parkinson's disease. We determined contact location using microelectrode recording (MER) and high-field 7T MRI, and assessed the relationship between impedance and contact location. For contact location as assessed via MER, impedance was significantly higher for contacts in STN, at baseline (111 Ω vs STN border, p=0.03; 169 Ω vs white matter, p<0.001) and over time (90 Ω vs STN border, p<0.001; 54 Ω vs white matter, p<0.001). Over time, impedance was lowest in contacts situated at STN border (p=0.03). Impedance did not vary by contact location as assessed via imaging. Location determination was 75% consistent between MER and imaging. Impedance was inversely related to absolute symptom reduction during stimulation (-2.5 motor portion of the Unified Parkinson's Disease Rating Scale (mUPDRS) points per 1000 Ω, p=0.01). In the vicinity of DBS electrodes chronically implanted in STN, impedance is lower at the rostral STN border and in white matter, than in STN. This finding suggests that current reaches white matter fibres more readily than neuronal cell bodies in STN, which may help explain anatomic variation in stimulation efficacy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  2. Atlas-based segmentation of deep brain structures using non-rigid registration

    NASA Astrophysics Data System (ADS)

    Khan, Muhammad Faisal; Mewes, Klaus; Gross, Robert E.; Škrinjar, Oskar

    2008-03-01

    Deep brain structures are frequently used as targets in neurosurgical procedures. However, the boundaries of these structures are often not visible in clinically used MR and CT images. Techniques based on anatomical atlases and indirect targeting are used to infer the location of these targets intraoperatively. Initial errors of such approaches may be up to a few millimeters, which is not negligible. E.g. subthalamic nucleus is approximately 4x6 mm in the axial plane and the diameter of globus pallidus internus is approximately 8 mm, both of which are used as targets in deep brain stimulation surgery. To increase the initial localization accuracy of deep brain structures we have developed an atlas-based segmentation method that can be used for the surgery planning. The atlas is a high resolution MR head scan of a healthy volunteer with nine deep brain structures manually segmented. The quality of the atlas image allowed for the segmentation of the deep brain structures, which is not possible from the clinical MR head scans of patients. The subject image is non-rigidly registered to the atlas image using thin plate splines to represent the transformation and normalized mutual information as a similarity measure. The obtained transformation is used to map the segmented structures from the atlas to the subject image. We tested the approach on five subjects. The quality of the atlas-based segmentation was evaluated by visual inspection of the third and lateral ventricles, putamena, and caudate nuclei, which are visible in the subject MR images. The agreement of these structures for the five tested subjects was approximately 1 to 2 mm.

  3. Beta oscillations in freely moving Parkinson's subjects are attenuated during deep brain stimulation.

    PubMed

    Quinn, Emma J; Blumenfeld, Zack; Velisar, Anca; Koop, Mandy Miller; Shreve, Lauren A; Trager, Megan H; Hill, Bruce C; Kilbane, Camilla; Henderson, Jaimie M; Brontë-Stewart, Helen

    2015-11-01

    Investigations into the effect of deep brain stimulation (DBS) on subthalamic (STN) beta (13-30 Hz) oscillations have been performed in the perioperative period with the subject tethered to equipment. Using an embedded sensing neurostimulator, this study investigated whether beta power was similar in different resting postures and during forward walking in freely moving subjects with Parkinson's disease (PD) and whether STN DBS attenuated beta power in a voltage-dependent manner. Subthalamic local field potentials were recorded from the DBS lead, using a sensing neurostimulator (Activa(®) PC+S, Medtronic, Inc., Food and Drug Administration- Investigational Device Exemption (IDE)-, institutional review board-approved) from 15 PD subjects (30 STNs) off medication during lying, sitting, and standing, during forward walking, and during randomized periods of 140 Hz DBS at 0 V, 1 V, and 2.5/3 V. Continuous video, limb angular velocity, and forearm electromyography recordings were synchronized with neural recordings. Data were parsed to avoid any movement or electrical artifact during resting states. Beta power was similar during lying, sitting, and standing (P = 0.077, n = 28) and during forward walking compared with the averaged resting state (P = 0.466, n = 24), although akinetic rigid PD subjects tended to exhibit decreased beta power when walking. Deep brain stimulation at 3 V and at 1 V attenuated beta power compared with 0 V (P < 0.003, n = 14), and this was voltage dependent (P < 0.001). Beta power was conserved during resting and forward walking states and was attenuated in a voltage-dependent manner during 140-Hz DBS. Phenotype may be an important consideration if this is used for closed-loop DBS. © 2015 International Parkinson and Movement Disorder Society.

  4. Modulation of gait coordination by subthalamic stimulation improves freezing of gait.

    PubMed

    Fasano, Alfonso; Herzog, Jan; Seifert, Elena; Stolze, Henning; Falk, Daniela; Reese, René; Volkmann, Jens; Deuschl, Günther

    2011-04-01

    The effect of subthalamic deep brain stimulation on gait coordination and freezing of gait in patients with Parkinson's disease is incompletely understood. The purpose of this study was to investigate the extent to which modulation of symmetry and coordination between legs by subthalamic deep brain stimulation alters the frequency and duration of freezing of gait in patients with Parkinson's disease. We recruited 13 post-subthalamic deep brain stimulation patients with Parkinson's disease with off freezing of gait and evaluated them in the following 4 conditions: subthalamic deep brain stimulation on (ON) and stimulation off (OFF), 50% reduction of stimulation voltage for the leg with shorter step length (worse side reduction) and for the leg with longer step length (better side reduction). Gait analysis was performed on a treadmill and recorded by an optoelectronic analysis system. We measured frequency and duration of freezing of gait episodes. Bilateral coordination of gait was assessed by the Phase Coordination Index, quantifying the ability to generate antiphase stepping. From the OFF to the ON state, freezing of gait improved in frequency (2.0 ± 0.4 to 1.4 ± 0.5 episodes) and duration (12.2 ± 2.6 to 2.6 ± 0.8 seconds; P = .005). Compared with the ON state, only better side reduction further reduced freezing of gait frequency (0.2 ± 0.2) and duration of episodes (0.2 ± 0.2 seconds; P = .03); worse side reduction did not change frequency (1.3 ± 0.4) but increased freezing of gait duration (5.2 ± 2.1 seconds). The better side reduction-associated improvements were accompanied by normalization of gait coordination, as measured by phase coordination index (16.5% ± 6.0%), which was significantly lower than in the other 3 conditions. Reduction of stimulation voltage in the side contralateral to the leg with longer step length improves frequency and duration of freezing of gait through normalization of gait symmetry and coordination in subthalamic deep brain

  5. Neuronal activity correlated with checking behaviour in the subthalamic nucleus of patients with obsessive-compulsive disorder.

    PubMed

    Burbaud, Pierre; Clair, Anne-Hélène; Langbour, Nicolas; Fernandez-Vidal, Sara; Goillandeau, Michel; Michelet, Thomas; Bardinet, Eric; Chéreau, Isabelle; Durif, Franck; Polosan, Mircea; Chabardès, Stephan; Fontaine, Denys; Magnié-Mauro, Marie-Noelle; Houeto, Jean-Luc; Bataille, Benoît; Millet, Bruno; Vérin, Marc; Baup, Nicolas; Krebs, Marie-Odile; Cornu, Philippe; Pelissolo, Antoine; Arbus, Christophe; Simonetta-Moreau, Marion; Yelnik, Jérôme; Welter, Marie-Laure; Mallet, Luc

    2013-01-01

    Doubt, and its behavioural correlate, checking, is a normal phenomenon of human cognition that is dramatically exacerbated in obsessive-compulsive disorder. We recently showed that deep brain stimulation in the associative-limbic area of the subthalamic nucleus, a central core of the basal ganglia, improved obsessive-compulsive disorder. To understand the physiological bases of symptoms in such patients, we recorded the activity of individual neurons in the therapeutic target during surgery while subjects performed a cognitive task that gave them the possibility of unrestricted repetitive checking after they had made a choice. We postulated that the activity of neurons in this region could be influenced by doubt and checking behaviour. Among the 63/87 task-related neurons recorded in 10 patients, 60% responded to various combinations of instructions, delay, movement or feedback, thus highlighting their role in the integration of different types of information. In addition, task-related activity directed towards decision-making increased during trials with checking in comparison with those without checking. These results suggest that the associative-limbic subthalamic nucleus plays a role in doubt-related repetitive thoughts. Overall, our results not only provide new insight into the role of the subthalamic nucleus in human cognition but also support the fact that subthalamic nucleus modulation by deep brain stimulation reduced compulsive behaviour in patients with obsessive-compulsive disorder.

  6. Pallidotomy after chronic deep brain stimulation.

    PubMed

    Bulluss, Kristian J; Pereira, Erlick A; Joint, Carole; Aziz, Tipu Z

    2013-11-01

    Recent publications have demonstrated that deep brain stimulation for Parkinson's disease still exerts beneficial effects on tremor, rigidity, and bradykinesia for up to 10 years after implantation of the stimulator. However with the progression of Parkinson's disease, features such as cognitive decline or "freezing" become prominent, and the presence of an implanted and functioning deep brain stimulator can impose a profound burden of care on the clinical team and family. The authors describe their experience in treating 4 patients who underwent removal of the implanted device due to either progressive dementia requiring full-time nursing or due to infection, and who subsequently underwent a unilateral pallidotomy.

  7. Quantification and visualization of the three-dimensional inconsistency of the subthalamic nucleus in the Schaltenbrand-Wahren brain atlas.

    PubMed

    Nowinski, Wieslaw L; Liu, Jimin; Thirunavuukarasuu, A

    2006-01-01

    The Schaltenbrand-Wahren (SW) brain atlas has many limitations: the major two are three-dimensional (3D) inconsistency and spatial sparseness. In this work, we quantify and visualize the 3D inconsistency of the subthalamic nucleus (STN). The STN 3D models, 3D-A, 3D-C and 3D-S, are reconstructed from the SW axial, coronal, and sagittal microseries, respectively, by using a shape-based (NURBS) approach. All three models are placed in the SW coordinate system and compared quantitatively in terms of location (centroids), size (volumes), shape (normalized eigenvalues), orientation (eigenvectors), and mutual spatial relationships (overlaps and inclusions). Analysis is done in 3D within each orientation and across them. A dedicated tool is developed for quantitative validation of 3D modeling. The average error achieved is 0.088 mm, which is at the resolution limit of the digital SW atlas. The reconstructed 3D STN models differ in location, size, shape, orientation, overlap size, and inclusion rate. The 3D-S volume is 1.27 times larger than that of 3D-A and 1.38 times larger than that of 3D-C. The highest overlap size is found between 3D-A and 3D-S. The highest inclusion rates of 52.5 and 66.6% are for 3D-A and 3D-S. 3D-C has the lowest overlap size and results in the lowest inclusion rates (around 20-30%), meaning that 3D-C is substantially displaced in comparison to 3D-A and 3D-S. The lateral centroid coordinate of 3D-C is 9.18 mm while that of 3D-S is 12.17 mm. Each of the 3D models has some limitation: 3D-A in orientation, 3D-C in location, and 3D-S in shape realism. The STN in comparison to the actual almond is smaller, and relatively (i.e. normalized to the same height) 2.2-2.4 times wider and 3.7-5.5 times longer. 3D-C becomes more similar to 3D-S by scaling the SW coronal microseries laterally by 1.3257. Then the lateral coordinates of their centroids coincide, the difference between them in orientation is 0.11 mm, and 3D-S is only 1.06 times larger than the scaled

  8. Subthalamic nucleus phase–amplitude coupling correlates with motor impairment in Parkinson’s disease

    PubMed Central

    van Wijk, Bernadette C.M.; Beudel, Martijn; Jha, Ashwani; Oswal, Ashwini; Foltynie, Tom; Hariz, Marwan I.; Limousin, Patricia; Zrinzo, Ludvic; Aziz, Tipu Z.; Green, Alexander L.; Brown, Peter; Litvak, Vladimir

    2016-01-01

    Objective High-amplitude beta band oscillations within the subthalamic nucleus are frequently associated with Parkinson’s disease but it is unclear how they might lead to motor impairments. Here we investigate a likely pathological coupling between the phase of beta band oscillations and the amplitude of high-frequency oscillations around 300 Hz. Methods We analysed an extensive data set comprising resting-state recordings obtained from deep brain stimulation electrodes in 33 patients before and/or after taking dopaminergic medication. We correlated mean values of spectral power and phase–amplitude coupling with severity of hemibody bradykinesia/rigidity. In addition, we used simultaneously recorded magnetoencephalography to look at functional interactions between the subthalamic nucleus and ipsilateral motor cortex. Results Beta band power and phase–amplitude coupling within the subthalamic nucleus correlated positively with severity of motor impairment. This effect was more pronounced within the low-beta range, whilst coherence between subthalamic nucleus and motor cortex was dominant in the high-beta range. Conclusions We speculate that the beta band might impede pro-kinetic high-frequency activity patterns when phase–amplitude coupling is prominent. Furthermore, results provide evidence for a functional subdivision of the beta band into low and high frequencies. Significance Our findings contribute to the interpretation of oscillatory activity within the cortico-basal ganglia circuit. PMID:26971483

  9. Subthalamic Neurons Encode Both Single- and Multi-Limb Movements in Parkinson’s Disease Patients

    PubMed Central

    Tankus, Ariel; Strauss, Ido; Gurevich, Tanya; Mirelman, Anat; Giladi, Nir; Fried, Itzhak; Hausdorff, Jeffrey M.

    2017-01-01

    The subthalamic nucleus (STN) is the main target for neurosurgical treatment of motor signs of Parkinson’s disease (PD). Despite the therapeutic effect on both upper and lower extremities, its role in motor control and coordination and its changes in Parkinson’s disease are not fully clear. We intraoperatively recorded single unit activity in ten patients with PD who performed repetitive feet or hand movements while undergoing implantation of a deep brain stimulator. We found both distinct and overlapping representations of upper and lower extremity movement kinematics in subthalamic units and observed evidence for re-routing to a multi-limb representation that participates in limb coordination. The well-known subthalamic somatotopy showed a large overlap of feet and hand representations in the PD patients. This overlap and excessive amounts of kinematics or coordination units may reflect pathophysiology or compensatory mechanisms. Our findings thus explain, at the single neuron level, the important subthalamic role in motor control and coordination and indicate the effect of PD on the neuronal representation of movement. PMID:28211850

  10. Perfusion brain SPECT in assessing motor improvement after deep brain stimulation in Parkinson's disease.

    PubMed

    Paschali, Anna; Constantoyannis, Constantinos; Angelatou, Fevronia; Vassilakos, Pavlos

    2013-03-01

    High-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become an established therapeutic approach for the management of patients with late-stage idiopathic Parkinson's disease (PD). The aim of the present study was to assess regional cerebral blood flow (rCBF) changes related to motor improvement. Twenty-one PD patients underwent two rCBF SPECT studies at rest, once preoperatively in the off-meds state and the other postoperatively (at 6 ± 2 months) in the off medication/on stimulation state. Patients were classified according to the UPDRS and H&Y scale. NeuroGam software was used to register, quantify, and compare two sequential brain SPECT studies of the same patient in order to investigate rCBF changes during STN stimulation in comparison with preoperative rCBF. The relationship between rCBF and UPDRS scores was used as a covariate of interest. Twenty patients showed clinical improvement during the first months after surgery, resulting in a 44 % reduction of the UPDRS motor score. The administered mean daily levodopa dose significantly decreased from 850 ± 108 mg before surgery to 446 ± 188 mg during the off-meds state (p < 0.001, paired t test). At the 6-month postoperative assessment, we noticed rCBF increases in the pre-supplementary motor area (pre-SMA) and the premotor cortex (PMC) (mean rCBF increase = 10.2 %, p < 0.05), the dorsolateral prefrontal cortex and in associative and limbic territories of the frontal cortex (mean rCBF increase = 8.2 %, p > 0.05). A correlation was detected between the improvement in motor scores and the rCBF increase in the pre-SMA and PMC (r = 0.89, p < 0.001). Our study suggests that STN stimulation leads to improvement in neural activity and rCBF increase in higher-order motor cortical areas.

  11. Ultra-High Field MRI Post Mortem Structural Connectivity of the Human Subthalamic Nucleus, Substantia Nigra, and Globus Pallidus

    PubMed Central

    Plantinga, Birgit R.; Roebroeck, Alard; Kemper, Valentin G.; Uludağ, Kâmil; Melse, Maartje; Mai, Jürgen; Kuijf, Mark L.; Herrler, Andreas; Jahanshahi, Ali; ter Haar Romeny, Bart M.; Temel, Yasin

    2016-01-01

    Introduction: The subthalamic nucleus, substantia nigra, and globus pallidus, three nuclei of the human basal ganglia, play an important role in motor, associative, and limbic processing. The network of the basal ganglia is generally characterized by a direct, indirect, and hyperdirect pathway. This study aims to investigate the mesoscopic nature of these connections between the subthalamic nucleus, substantia nigra, and globus pallidus and their surrounding structures. Methods: A human post mortem brain specimen including the substantia nigra, subthalamic nucleus, and globus pallidus was scanned on a 7 T MRI scanner. High resolution diffusion weighted images were used to reconstruct the fibers intersecting the substantia nigra, subthalamic nucleus, and globus pallidus. The course and density of these tracks was analyzed. Results: Most of the commonly established projections of the subthalamic nucleus, substantia nigra, and globus pallidus were successfully reconstructed. However, some of the reconstructed fiber tracks such as the connections of the substantia nigra pars compacta to the other included nuclei and the connections with the anterior commissure have not been shown previously. In addition, the quantitative tractography approach showed a typical degree of connectivity previously not documented. An example is the relatively larger projections of the subthalamic nucleus to the substantia nigra pars reticulata when compared to the projections to the globus pallidus internus. Discussion: This study shows that ultra-high field post mortem tractography allows for detailed 3D reconstruction of the projections of deep brain structures in humans. Although the results should be interpreted carefully, the newly identified connections contribute to our understanding of the basal ganglia. PMID:27378864

  12. Deep brain stimulation mechanisms: beyond the concept of local functional inhibition.

    PubMed

    Deniau, Jean-Michel; Degos, Bertrand; Bosch, Clémentine; Maurice, Nicolas

    2010-10-01

    Deep brain electrical stimulation has become a recognized therapy in the treatment of a variety of motor disorders and has potentially promising applications in a wide range of neurological diseases including neuropsychiatry. Behavioural observation that electrical high-frequency stimulation of a given brain area induces an effect similar to a lesion suggested a mechanism of functional inhibition. In vitro and in vivo experiments as well as per operative recordings in patients have revealed a variety of effects involving local changes of neuronal excitability as well as widespread effects throughout the connected network resulting from activation of axons, including antidromic activation. Here we review current data regarding the local and network activity changes induced by high-frequency stimulation of the subthalamic nucleus and discuss this in the context of motor restoration in Parkinson's disease. Stressing the important functional consequences of axonal activation in deep brain stimulation mechanisms, we highlight the importance of developing anatomical knowledge concerning the fibre connections of the putative therapeutic targets.

  13. Cortical magnetoencephalography of deep brain stimulation for the treatment of postural tremor.

    PubMed

    Connolly, Allison T; Bajwa, Jawad A; Johnson, Matthew D

    2012-10-01

    The effects of deep brain stimulation (DBS) on motor cortex circuitry in Essential tremor (ET) and Parkinson's disease (PD) patients are not well understood, in part, because most imaging modalities have difficulty capturing and localizing motor cortex dynamics on the same temporal scale as motor symptom expression. Here, we report on the use of magnetoencephalography (MEG) to characterize sources of postural tremor activity within the brain of an ET/PD patient and the effects of bilateral subthalamic nucleus DBS on these sources. Recordings were performed during unilateral and bilateral DBS at stimulation amplitudes of 0 V, 1 V, and 3 V corresponding to no therapy, subtherapeutic, and therapeutic configurations, respectively. Dipole source localization in reference to the postural tremor frequency recorded with electromyography (EMG) showed prominent sources in both right and left motor cortices when no therapy was provided. These sources dissipated as the amplitude of stimulation increased to a therapeutic level (P = 0.0062). Coherence peaks between the EMG and MEG recordings were seen at both 4 Hz, postural tremor frequency, and at 8 Hz, twice the tremor frequency, with no therapy. Both peaks were reduced with therapeutic DBS. These results demonstrate the capabilities of MEG to record cortical dynamics of tremor during deep brain stimulation and suggest that MEG could be used to examine DBS in the context of motor symptoms of PD and of ET.

  14. The subthalamic nucleus modulates the early phase of probabilistic classification learning.

    PubMed

    Weiss, Daniel; Lam, Judith M; Breit, Sorin; Gharabaghi, Alireza; Krüger, Rejko; Luft, Andreas R; Wächter, Tobias

    2014-07-01

    Previous models proposed that the subthalamic nucleus (STN) is critical in the early phase of skill acquisition. We hypothesized that subthalamic deep brain stimulation modulates the learning curve in early classification learning. Thirteen idiopathic Parkinson's disease patients (iPD) with subthalamic deep brain stimulation (STN-DBS), 9 medically treated iPD, and 21 age-matched healthy controls were tested with a probabilistic classification task. STN-DBS patients were tested with stimulation OFF and ON, and medically treated patients with medication OFF and ON, respectively. Performance and reaction time were analyzed on the first 100 consecutive trials as early learning phase. Moreover, data were separated for low and high-probability patterns, and more differentiated strategy analyses were used. The major finding was a significant modulation of the learning curve in DBS patients with stimulation ON: although overall learning was similar to healthy controls, only the stimulation ON group showed a transient significant performance dip from trials '41-60' that rapidly recovered. Further analysis indicated that this might be paralleled by a modulation of the learning strategy, particularly on the high-probability patterns. The reaction time was unchanged during the dip. Our study supports that the STN serves as a relay in early classification learning and directs attention toward unacquainted content. The STN might play a role in balancing the short-term success against strategy optimization for improved long-term outcome.

  15. Microelectrode targeting of the subthalamic nucleus for deep brain stimulation surgery.

    PubMed

    Montgomery, Erwin B

    2012-09-15

    Though microelectrode recordings likely increase the risks and costs of DBS, incremental improvement in accuracy may translate into improved outcomes that justify these risks and costs. Clinically based, controlled studies to resolve these issues are problematic. Until such studies are reported, physicians must rely on indirect evidence. The spatial variability of physiologically defined optimal targets, as determined by microelectrode recording (MER), necessary for targeting the STN was calculated. Study of the effectiveness of a MER algorithm was based on the number of penetrations required. The radius of the volume with a 99% chance of including the physiologically defined optimal target, based on 108 cases, was 4.5 mm. This is larger than the estimated radius of the DBS effect, which is variously estimated to be 2 to 3.9 mm. The 99% confidence radius in the plane orthogonal to the lead was 3.2 mm. In 70% of cases, the imaging-based trajectories corresponded to the physiologically defined optimal target. For the remaining 30% of cases, 70% required only a single additional MER tract. The radii of the 99% confidence volume and area may be larger than the effective radius of stimulation. Surveying within those volumes or areas is therefore necessary to assure that at least 99% of cases will cover the physiologically defined target. The MER algorithm was robust in detecting the physiologically defined optimal target. However, there are significant caveats in interpretation of the data.

  16. Predicting the effects of deep brain stimulation with diffusion tensor based electric field models.

    PubMed

    Butson, Christopher R; Cooper, Scott E; Henderson, Jaimie M; McIntyre, Cameron C

    2006-01-01

    Deep brain stimulation (DBS) is an established therapy for the treatment of movement disorders, and has shown promising results for the treatment of a wide range of other neurological disorders. However, little is known about the mechanism of action of DBS or the volume of brain tissue affected by stimulation. We have developed methods that use anatomical and diffusion tensor MRI (DTI) data to predict the volume of tissue activated (VTA) during DBS. We co-register the imaging data with detailed finite element models of the brain and stimulating electrode to enable anatomically and electrically accurate predictions of the spread of stimulation. One critical component of the model is the DTI tensor field that is used to represent the 3-dimensionally anisotropic and inhomogeneous tissue conductivity. With this system we are able to fuse structural and functional information to study a relevant clinical problem: DBS of the subthalamic nucleus for the treatment of Parkinsons disease (PD). Our results show that inclusion of the tensor field in our model caused significant differences in the size and shape of the VTA when compared to a homogeneous, isotropic tissue volume. The magnitude of these differences was proportional to the stimulation voltage. Our model predictions are validated by comparing spread of predicted activation to observed effects of oculomotor nerve stimulation in a PD patient. In turn, the 3D tissue electrical properties of the brain play an important role in regulating the spread of neural activation generated by DBS.

  17. Relation of lead trajectory and electrode position to neuropsychological outcomes of subthalamic neurostimulation in Parkinson's disease: results from a randomized trial.

    PubMed

    Witt, Karsten; Granert, Oliver; Daniels, Christine; Volkmann, Jens; Falk, Daniela; van Eimeren, Thilo; Deuschl, Günther

    2013-07-01

    Deep brain stimulation of the subthalamic nucleus improves motor functions in patients suffering from advanced Parkinson's disease but in some patients, it is also associated with a mild decline in cognitive functioning about one standard deviation from the preoperative state. We assessed the impact of the cortical lead entry point, the subcortical electrode path and the position of the active electrode contacts on neuropsychological changes after subthalamic nucleus-deep brain stimulation compared to a control group of patients receiving best medical treatment. Sixty-eight patients with advanced Parkinson's disease were randomly assigned to have subthalamic nucleus-deep brain stimulation or best medical treatment for Parkinson's disease. All patients had a blinded standardized neuropsychological exam (Mattis Dementia Rating scale, backward digit span, verbal fluency and Stroop task performance) at baseline and after 6 months of treatment. Patients with subthalamic nucleus-deep brain stimulation were defined as impaired according to a mild decline of one or more standard deviations compared to patients in the best medical treatment group. The cortical entry point of the electrodes, the electrode trajectories and the position of the active electrode contact were transferred into a normalized brain volume by an automated, non-linear registration algorithm to allow accurate statistical group analysis using pre- and postoperative magnetic resonance imaging data. Data of 31 patients of the subthalamic nucleus-deep brain stimulation group and 31 patients of the best medical treatment group were analysed. The subthalamic nucleus-deep brain stimulation group showed impaired semantic fluency compared with the best medical treatment group 6 months after surgery (P = 0.02). Electrode trajectories intersecting with caudate nuclei increased the risk of a decline in global cognition and working memory performance. Statistically, for every 0.1 ml overlap with a caudate nucleus

  18. A Novel Lead Design for Modulation and Sensing of Deep Brain Structures

    PubMed Central

    Connolly, Allison T.; Vetter, Rio J.; Hetke, Jamille F.; Teplitzky, Benjamin A.; Kipke, Daryl R.; Pellinen, David S.; Anderson, David J.; Baker, Kenneth B.; Vitek, Jerrold L.; Johnson, Matthew D.

    2016-01-01

    Goal Develop and characterize the functionality of a novel thin-film probe technology with a higher density of electrode contacts than are currently available with commercial deep brain stimulation (DBS) lead technology. Such technology has potential to enhance the spatial precision of DBS and enable a more robust approach to sensing local field potential activity in the context of adaptive DBS strategies. Methods Thin-film planar arrays were microfabricated and then assembled on a cylindrical carrier to achieve a lead with 3D conformation. Using an integrated and removable stylet, the arrays were chronically implanted in the subthalamic nucleus and globus pallidus in two parkinsonian non-human primates. Results This study provides the first in vivo data from chronically implanted DBS arrays for translational non-human primate studies. Stimulation through the arrays induced a decrease in parkinsonian rigidity, and directing current around the lead showed an orientation dependency for eliciting motor capsule side effects. The array recordings also showed that oscillatory activity in the basal ganglia is heterogeneous at a smaller scale than detected by current DBS lead technology. Conclusion These 3D DBS arrays provide an enabling tool for future studies that seek to monitor and modulate deep brain activity through chronically implanted leads. Significance DBS lead technology with a higher density of electrode contacts have potential to enable sculpting DBS current flow and sensing biomarkers of disease and therapy. PMID:26529747

  19. Non-Infectious Peri-Electrode Edema and Contrast Enhancement Following Deep Brain Stimulation Surgery.

    PubMed

    Arocho-Quinones, Elsa V; Pahapill, Peter A

    2016-12-01

    Dramatic radiographic abnormalities seen after electrode placement (DRAAEP) in deep brain stimulation (DBS) surgery is rare and it has not been associated with infection or hemorrhage. It has consisted of peri-electrode low-attenuation signals on CT scans and extensive T2-hyperintense signals without associated contrast enhancement (CE) on MRI scans. Report on the management of a patient with Parkinson's disease (PD) presenting with a seizure and findings of DRAAEP with positive CE 12 days after the placement of a subthalamic nucleus (STN) DBS electrode. Head CT and contrasted brain MRI scans were completed on presentation. Standard laboratory work up was obtained to evaluate for infection. Operative exploration deep to the burr-hole site surrounding the electrode was performed and cultures were obtained. Serial contrasted MRI scans were completed to determine the abnormal signal duration. A MRI revealed extensive T2-hyperintensity and positive CE concentrated around the burr-hole site surrounding the electrode. Intraoperative exploration revealed no evidence of infection and electrode revision was avoided. There was near resolution of the abnormal T2 signal and CE at six weeks from detection. The patient remained without signs of intracranial infection and responded well to DBS. To our knowledge, this is the first reported case of DRAAEP with positive gadolinium enhancement. Despite the extensive contrast enhancement, these DRAAEP appear to remain benign transient events that, in the absence of clinical signs of infection or neurologic decline, may warrant no further aggressive intervention such as hardware removal. © 2016 International Neuromodulation Society.

  20. Optogenetics and deep brain stimulation neurotechnologies.

    PubMed

    Kondabolu, Krishnakanth; Kowalski, Marek Mateusz; Roberts, Erik Andrew; Han, Xue

    2015-01-01

    Brain neural network is composed of densely packed, intricately wired neurons whose activity patterns ultimately give rise to every behavior, thought, or emotion that we experience. Over the past decade, a novel neurotechnique, optogenetics that combines light and genetic methods to control or monitor neural activity patterns, has proven to be revolutionary in understanding the functional role of specific neural circuits. We here briefly describe recent advance in optogenetics and compare optogenetics with deep brain stimulation technology that holds the promise for treating many neurological and psychiatric disorders.

  1. [Deep brain stimulation for psychiatric disorders].

    PubMed

    Overbeek, Jozefien M; de Koning, Pelle P; Luigjes, Judy; van den Munckhof, Pepijn; Schuurman, P R Richard; Denys, Damiaan

    2013-01-01

    Deep brain stimulation (DBS) is a treatment using implanted electrodes to deliver electrical pulses to targeted areas of the brain. DBS holds great promise in psychiatry for the treatment of patients with treatment-resistant obsessive-compulsive disorder, depression and Gilles de la Tourette syndrome. Double-blind and open trials have shown that the treatment is effective in about half of these patients. Further research should focus on optimizing DBS with respect to target location for the various psychiatric disorders. More controlled double-blind trials are needed to corroborate the effectiveness of DBS in patients with psychiatric disorders.

  2. Randomized trial of deep brain stimulation for Parkinson disease: thirty-six-month outcomes; turning tables: should GPi become the preferred DBS target for Parkinson disease?

    PubMed

    Montgomery, Erwin B

    2013-01-08

    Weaver et al. and Tagliati mistakenly infer clinical equivalence between globus pallidus interna vs subthalamic nucleus deep brain stimulation based on failure to demonstrate statistically significant differences. A clinically meaningful-not statistically significant-difference in outcome should be decided a priori, after which the sample size necessary to have a reasonable probability of detecting the difference could be determined. (4) Fortunately, the study by Weaver et al. had sufficient sample size to demonstrate a 1-point difference in motor outcomes. However, such comparisons presume optimal management so as not to produce a "ceiling effect" that would obscure differences.

  3. Deep brain stimulation of CM/PF of thalamus could be the new elective target for tremor in advanced Parkinson's Disease?

    PubMed

    Peppe, A; Gasbarra, A; Stefani, A; Chiavalon, C; Pierantozzi, M; Fermi, E; Stanzione, P; Caltagirone, C; Mazzone, P

    2008-08-01

    Aim of this study was to investigate whether Deep Brain Stimulation (DBS) of the Centre Median Nucleus/Parafascicular (CM/PF) Complex is useful in reducing extrapyramidal symptoms in advanced Parkinson's Disease (PD) patients. In particular, we compared the action of CM/PF and subthalamic nucleus (STN) DBS on resting hand tremor using EMG surface of ulnar and radial right-hand muscles. Our results show that C/M DBS is very effective in reducing tremor, indicating this complex as a new target in advanced PD patients.

  4. Deep brain stimulation exacerbates hypokinetic dysarthria in a rat model of Parkinson's disease.

    PubMed

    King, Nathaniel O; Anderson, Collin J; Dorval, Alan D

    2016-02-01

    Motor symptoms of Parkinson's disease (PD) follow the degeneration of dopaminergic neurons in the substantia nigra pars compacta. Deep brain stimulation (DBS) treats some parkinsonian symptoms, such as tremor, rigidity, and bradykinesia, but may worsen certain medial motor symptoms, including hypokinetic dysarthria. The mechanisms by which DBS exacerbates dysarthria while improving other symptoms are unclear and difficult to study in human patients. This study proposes an animal model of DBS-exacerbated dysarthria. We use the unilateral, 6-hydroxydopamine (6-OHDA) rat model of PD to test the hypothesis that DBS exacerbates quantifiable aspects of vocalization. Mating calls were recorded from sexually experienced male rats under healthy and parkinsonian conditions and during DBS of the subthalamic nucleus. Relative to healthy rats, parkinsonian animals made fewer calls with shorter and less complex vocalizations. In the parkinsonian rats, putatively therapeutic DBS further reduced call frequency, duration, and complexity. The individual utterances of parkinsonian rats spanned a greater bandwidth than those of healthy rats, potentially reducing the effectiveness of the vocal signal. This utterance bandwidth was further increased by DBS. We propose that the parkinsonism-associated changes in call frequency, duration, complexity, and dynamic range combine to constitute a rat analog of parkinsonian dysarthria. Because DBS exacerbates the parkinsonism-associated changes in each of these metrics, the subthalamic stimulated 6-OHDA rat is a good model of DBS-induced hypokinetic dysarthria in PD. This model will help researchers examine how DBS alleviates many motor symptoms of PD while exacerbating parkinsonian speech deficits that can greatly diminish patient quality of life.

  5. Deep Brain Stimulation Exacerbates Hypokinetic Dysarthria in a Rat Model of Parkinson's Disease

    PubMed Central

    King, Nathaniel O.; Anderson, Collin J.; Dorval, Alan D.

    2015-01-01

    Motor symptoms of Parkinson's disease (PD) follow the degeneration of dopaminergic neurons in the substantia nigra pars compacta. Deep brain stimulation (DBS) treats some parkinsonian symptoms – tremor, rigidity, and bradykinesia – but may worsen certain medial motor symptoms, including hypokinetic dysarthria. The mechanisms by which DBS exacerbates dysarthria while improving other symptoms are unclear and difficult to study in human patients. In this work, we propose an animal model of DBS-exacerbated dysarthria. We used the unilateral, 6-hydroxydopamine rat model of PD to test the hypothesis that DBS exacerbates quantifiable aspects of vocalization. Mating calls were recorded from sexually-experienced male rats under healthy and parkinsonian conditions, and during DBS of the subthalamic nucleus. Relative to healthy rats, parkinsonian animals made fewer calls with shorter and less complex vocalizations. In the parkinsonian rats, putatively therapeutic DBS further reduced call frequency, duration, and complexity. Interestingly, the individual utterances of parkinsonian rats spanned a greater bandwidth than those of healthy rats, potentially reducing the effectiveness of the vocal signal. This utterance bandwidth was further increased by DBS. We propose that the parkinsonism-associated changes in call frequency, duration, complexity, and dynamic range combine to constitute a rat analog of parkinsonian dysarthria. Because DBS exacerbates the parkinsonism-associated changes in each of these metrics, the subthalamic stimulated 6-hydroxydopamine rat is a good model of DBS-induced hypokinetic dysarthria in PD. This model will help researchers examine how DBS alleviates many motor symptoms of PD, while exacerbating parkinsonian speech deficits that can greatly diminish patient quality of life. PMID:26498277

  6. The relationship between clinical phenotype and early staged bilateral deep brain stimulation in Parkinson disease.

    PubMed

    Sung, Victor W; Watts, Ray L; Schrandt, Christian J; Guthrie, Stephanie; Wang, Deli; Amara, Amy W; Guthrie, Barton L; Walker, Harrison C

    2013-12-01

    While many centers place bilateral deep brain stimulation (DBS) systems simultaneously, unilateral subthalamic nucleus (STN) DBS followed by a staged contralateral procedure has emerged as a treatment option for many patients. However, little is known about whether the preoperative phenotype predicts when staged placement of a DBS electrode in the opposite STN will be required. The authors aimed to determine whether preoperative clinical phenotype predicts early staged placement of a second STN DBS electrode in patients who undergo unilateral STN DBS for Parkinson disease (PD). Eighty-two consecutive patients with advanced PD underwent unilateral STN DBS contralateral to the most affected hemibody and had at least 2 years of follow-up. Multivariate logistic regression analysis determined preoperative characteristics that predicted staged placement of a second electrode in the opposite STN. Preoperative measurements included aspects of the Unified Parkinson's Disease Rating Scale (UPDRS), motor asymmetry index, and body weight. At 2-year follow-up, 28 (34%) of the 82 patients had undergone staged placement of a contralateral electrode while the remainder chose to continue with unilateral stimulation. Statistically significant improvements in UPDRS total and Part 3 scores were retained at the end of the 2-year follow-up period in both subsets of patients. Multivariate logistic regression analysis showed that the most important predictors for early staged placement of a second subthalamic stimulator were low asymmetry index (OR 13.4, 95% CI 2.8-64.9), high tremor subscore (OR 7.2, CI 1.5-35.0), and low body weight (OR 5.5, 95% CI 1.4-22.3). This single-center study provides evidence that elements of the preoperative PD phenotype predict whether patients will require early staged bilateral STN DBS. These data may aid in the management of patients with advanced PD who undergo STN DBS.

  7. Tremor Reduction by Deep Brain Stimulation Is Associated With Gamma Power Suppression in Parkinson's Disease

    PubMed Central

    Beudel, Martijn; Little, Simon; Pogosyan, Alek; Ashkan, Keyoumars; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Hariz, Marwan; Bogdanovic, Marko; Cheeran, Binith; Green, Alexander L.; Aziz, Tipu; Thevathasan, Wesley

    2015-01-01

    Objectives Rest tremor is a cardinal symptom of Parkinson's disease (PD), and is readily suppressed by deep brain stimulation (DBS) of the subthalamic nucleus (STN). The therapeutic effect of the latter on bradykinesia and rigidity has been associated with the suppression of exaggerated beta (13–30 Hz) band synchronization in the vicinity of the stimulating electrode, but there is no correlation between beta suppression and tremor amplitude. In the present study, we investigate whether tremor suppression is related to suppression of activities at other frequencies. Materials and Methods We recorded hand tremor and contralateral local field potential (LFP) activity from DBS electrodes during stimulation of the STN in 15 hemispheres in 11 patients with PD. DBS was applied with increasing voltages starting at 0.5 V until tremor suppression was achieved or until 4.5 V was reached. Results Tremor was reduced to 48.9% ± 10.9% of that without DBS once stimulation reached 2.5–3 V (t14 = −4.667, p < 0.001). There was a parallel suppression of low gamma (31–45 Hz) power to 92.5% ± 3% (t14 = −2.348, p = 0.034). This was not seen over a band containing tremor frequencies and their harmonic (4–12 Hz), or over the beta band. Moreover, low gamma power correlated with tremor severity (mean r = 0.43 ± 0.14, p = 0.008) within subjects. This was not the case for LFP power in the other two bands. Conclusions Our findings support a relationship between low gamma oscillations and PD tremor, and reinforce the principle that the subthalamic LFP is a rich signal that may contain information about the severity of multiple different Parkinsonian features. PMID:25879998

  8. Pathways of Translation: Deep Brain Stimulation

    PubMed Central

    Greenberg, Alexandra J.; Wahegaonkar, Abhijeet L.; Lee, Kendall H.

    2013-01-01

    Abstract Electrical stimulation of the brain has a 2000 year history. Deep brain stimulation (DBS), one form of neurostimulation, is a functional neurosurgical approach in which a high‐frequency electrical current stimulates targeted brain structures for therapeutic benefit. It is an effective treatment for certain neuropathologic movement disorders and an emerging therapy for psychiatric conditions and epilepsy. Its translational journey did not follow the typical bench‐to‐bedside path, but rather reversed the process. The shift from ancient and medieval folkloric remedy to accepted medical practice began with independent discoveries about electricity during the 19th century and was fostered by technological advances of the 20th. In this paper, we review that journey and discuss how the quest to expand its applications and improve outcomes is taking DBS from the bedside back to the bench. PMID:24330698

  9. Effect of deep brain stimulation and L-Dopa on electrocortical rhythms related to movement in Parkinson's disease.

    PubMed

    Devos, D; Defebvre, L

    2006-01-01

    In the early stages of Parkinson's disease (PD), impaired motor preparation has been related to a decrease in the latency of mu rhythm event-related desynchronisation (ERD) compared with control subjects, suggesting hypo activation of the contralateral, primary sensorimotor (PSM) cortex. Following movement, a decrease in amplitude of beta rhythm ERS was observed over the same region and thought to be related to impairment in cortical deactivation. By monitoring ERD/ERS, we aimed (i) to extend to advanced PD the observations made in less-advanced parkinsonism and (ii) to test the effect of acute L-Dopa, internal pallidal or subthalamic stimulation on these abnormalities. For the clinical evaluation the motor score of UPDRS decreased by about 60% under subthalamic stimulation and following acute L-Dopa administration and by 40% under internal pallidal stimulation. The following concurrent ERD/ERS changes under subthalamic stimulation and L-Dopa were observed: a marked increase in mu ERD latency during movement preparation over contralateral central region; an increase in mu ERD during movement execution over bilateral central regions; a decrease in mu ERD latency over bilateral frontocentral region and an increase in beta ERS over contralateral central region after movement. On the contrary, mu ERD latency was not improved under internal pallidal stimulation. Changes of mu and beta rhythm parameters seemed to be inversely correlated with bradykinesia. Mu rhythm ERD latency and the beta ERS amplitude further decreased in advanced PD compared with early stages, suggesting greater impairment of cortical activation/deactivation as the disease progresses and a partial restoration in relation to clinical improvement under treatments. Consequently, it appears that L-Dopa and deep brain stimulation partially restored the normal patterns of cortical oscillatory activity in PD, possibly by decreasing the low frequency hyper synchronisation at rest. This mechanism could be

  10. Assessing the direct effects of deep brain stimulation using embedded axon models

    NASA Astrophysics Data System (ADS)

    Sotiropoulos, Stamatios N.; Steinmetz, Peter N.

    2007-06-01

    To better understand the spatial extent of the direct effects of deep brain stimulation (DBS) on neurons, we implemented a geometrically realistic finite element electrical model incorporating anisotropic and inhomogenous conductivities. The model included the subthalamic nucleus (STN), substantia nigra (SN), zona incerta (ZI), fields of Forel H2 (FF), internal capsule (IC) and Medtronic 3387/3389 electrode. To quantify the effects of stimulation, we extended previous studies by using multi-compartment axon models with geometry and orientation consistent with anatomical features of the brain regions of interest. Simulation of axonal firing produced a map of relative changes in axonal activation. Voltage-controlled stimulation, with clinically typical parameters at the dorso-lateral STN, caused axon activation up to 4 mm from the target. This activation occurred within the FF, IC, SN and ZI with current intensities close to the average injected during DBS (3 mA). A sensitivity analysis of model parameters (fiber size, fiber orientation, degree of inhomogeneity, degree of anisotropy, electrode configuration) revealed that the FF and IC were consistently activated. Direct activation of axons outside the STN suggests that other brain regions may be involved in the beneficial effects of DBS when treating Parkinsonian symptoms.

  11. A multicentre study on suicide outcomes following subthalamic stimulation for Parkinson's disease

    PubMed Central

    Krack, Paul; Lang, Anthony E.; Lozano, Andres M.; Dujardin, Kathy; Schüpbach, Michael; D’Ambrosia, James; Thobois, Stephane; Tamma, Filippo; Herzog, Jan; Speelman, Johannes D.; Samanta, Johan; Kubu, Cynthia; Rossignol, Helene; Poon, Yu-Yan; Saint-Cyr, Jean A.; Ardouin, Claire; Moro, Elena

    2008-01-01

    Subthalamic nucleus deep brain stimulation improves motor symptoms and quality of life in advanced Parkinson's disease. As after other life-altering surgeries, suicides have been reported following deep brain stimulation for movement disorders. We sought to determine the suicide rate following subthalamic nucleus deep brain stimulation for Parkinson's disease by conducting an international multicentre retrospective survey of movement disorder and surgical centres. We further sought to determine factors associated with suicide attempts through a nested case-control study. In the survey of suicide rate, 55/75 centres participated. The completed suicide percentage was 0.45% (24/5311) and attempted suicide percentage was 0.90% (48/5311). Observed suicide rates in the first postoperative year (263/100 000/year) (0.26%) were higher than the lowest and the highest expected age-, gender- and country-adjusted World Health Organization suicide rates (Standardized Mortality Ratio for suicide: SMR 12.63–15.64; P < 0.001) and remained elevated at the fourth postoperative year (38/100 000/year) (0.04%) (SMR 1.81–2.31; P < 0.05). The excess number of deaths was 13 for the first postoperative year and one for the fourth postoperative year. In the case-control study of associated factors, 10 centres participated. Twenty-seven attempted suicides and nine completed suicides were compared with 70 controls. Postoperative depression (P < 0.001), being single (P = 0.007) and a previous history of impulse control disorders or compulsive medication use (P = 0.005) were independent associated factors accounting for 51% of the variance for attempted suicide risk. Attempted suicides were also associated (P < 0.05) with being younger, younger Parkinson's disease onset and a previous suicide attempt. Completed suicides were associated with postoperative depression (P < 0.001). Postoperative depression remained a significant factor associated with attempted and completed suicides after

  12. Balancing the Brain: Resting State Networks and Deep Brain Stimulation

    PubMed Central

    Kringelbach, Morten L.; Green, Alexander L.; Aziz, Tipu Z.

    2011-01-01

    Over the last three decades, large numbers of patients with otherwise treatment-resistant disorders have been helped by deep brain stimulation (DBS), yet a full scientific understanding of the underlying neural mechanisms is still missing. We have previously proposed that efficacious DBS works by restoring the balance of the brain's resting state networks. Here, we extend this proposal by reviewing how detailed investigations of the highly coherent functional and structural brain networks in health and disease (such as Parkinson's) have the potential not only to increase our understanding of fundamental brain function but of how best to modulate the balance. In particular, some of the newly identified hubs and connectors within and between resting state networks could become important new targets for DBS, including potentially in neuropsychiatric disorders. At the same time, it is of essence to consider the ethical implications of this perspective. PMID:21577250

  13. Deep learning for brain tumor classification

    NASA Astrophysics Data System (ADS)

    Paul, Justin S.; Plassard, Andrew J.; Landman, Bennett A.; Fabbri, Daniel

    2017-03-01

    Recent research has shown that deep learning methods have performed well on supervised machine learning, image classification tasks. The purpose of this study is to apply deep learning methods to classify brain images with different tumor types: meningioma, glioma, and pituitary. A dataset was publicly released containing 3,064 T1-weighted contrast enhanced MRI (CE-MRI) brain images from 233 patients with either meningioma, glioma, or pituitary tumors split across axial, coronal, or sagittal planes. This research focuses on the 989 axial images from 191 patients in order to avoid confusing the neural networks with three different planes containing the same diagnosis. Two types of neural networks were used in classification: fully connected and convolutional neural networks. Within these two categories, further tests were computed via the augmentation of the original 512×512 axial images. Training neural networks over the axial data has proven to be accurate in its classifications with an average five-fold cross validation of 91.43% on the best trained neural network. This result demonstrates that a more general method (i.e. deep learning) can outperform specialized methods that require image dilation and ring-forming subregions on tumors.

  14. Network effects of deep brain stimulation

    PubMed Central

    Alhourani, Ahmad; McDowell, Michael M.; Randazzo, Michael J.; Wozny, Thomas A.; Kondylis, Efstathios D.; Lipski, Witold J.; Beck, Sarah; Karp, Jordan F.; Ghuman, Avniel S.

    2015-01-01

    The ability to differentially alter specific brain functions via deep brain stimulation (DBS) represents a monumental advance in clinical neuroscience, as well as within medicine as a whole. Despite the efficacy of DBS in the treatment of movement disorders, for which it is often the gold-standard therapy when medical management becomes inadequate, the mechanisms through which DBS in various brain targets produces therapeutic effects is still not well understood. This limited knowledge is a barrier to improving efficacy and reducing side effects in clinical brain stimulation. A field of study related to assessing the network effects of DBS is gradually emerging that promises to reveal aspects of the underlying pathophysiology of various brain disorders and their response to DBS that will be critical to advancing the field. This review summarizes the nascent literature related to network effects of DBS measured by cerebral blood flow and metabolic imaging, functional imaging, and electrophysiology (scalp and intracranial electroencephalography and magnetoencephalography) in order to establish a framework for future studies. PMID:26269552

  15. Design, Fabrication, Simulation and Characterization of a Novel Dual-Sided Microelectrode Array for Deep Brain Recording and Stimulation.

    PubMed

    Zhao, Zongya; Gong, Ruxue; Huang, Hongen; Wang, Jue

    2016-06-15

    In this paper, a novel dual-sided microelectrode array is specially designed and fabricated for a rat Parkinson's disease (PD) model to study the mechanisms of deep brain stimulation (DBS). The fabricated microelectrode array can stimulate the subthalamic nucleus and simultaneously record electrophysiological information from multiple nuclei of the basal ganglia system. The fabricated microelectrode array has a long shaft of 9 mm and each planar surface is equipped with three stimulating sites (diameter of 100 μm), seven electrophysiological recording sites (diameter of 20 μm) and four sites with diameter of 50 μm used for neurotransmitter measurements in future work. The performances of the fabricated microelectrode array were characterized by scanning electron microscopy (SEM), electrochemical impedance spectroscopy (EIS) and cyclic voltammetry. In addition, the stimulating effects of the fabricated microelectrode were evaluated by finite element modeling (FEM). Preliminary animal experiments demonstrated that the designed microelectrode arrays can record spontaneous discharge signals from the striatum, the subthalamic nucleus and the globus pallidus interna. The designed and fabricated microelectrode arrays provide a powerful research tool for studying the mechanisms of DBS in rat PD models.

  16. Algorithmic design of a noise-resistant and efficient closed-loop deep brain stimulation system: A computational approach.

    PubMed

    Karamintziou, Sofia D; Custódio, Ana Luísa; Piallat, Brigitte; Polosan, Mircea; Chabardès, Stéphan; Stathis, Pantelis G; Tagaris, George A; Sakas, Damianos E; Polychronaki, Georgia E; Tsirogiannis, George L; David, Olivier; Nikita, Konstantina S

    2017-01-01

    Advances in the field of closed-loop neuromodulation call for analysis and modeling approaches capable of confronting challenges related to the complex neuronal response to stimulation and the presence of strong internal and measurement noise in neural recordings. Here we elaborate on the algorithmic aspects of a noise-resistant closed-loop subthalamic nucleus deep brain stimulation system for advanced Parkinson's disease and treatment-refractory obsessive-compulsive disorder, ensuring remarkable performance in terms of both efficiency and selectivity of stimulation, as well as in terms of computational speed. First, we propose an efficient method drawn from dynamical systems theory, for the reliable assessment of significant nonlinear coupling between beta and high-frequency subthalamic neuronal activity, as a biomarker for feedback control. Further, we present a model-based strategy through which optimal parameters of stimulation for minimum energy desynchronizing control of neuronal activity are being identified. The strategy integrates stochastic modeling and derivative-free optimization of neural dynamics based on quadratic modeling. On the basis of numerical simulations, we demonstrate the potential of the presented modeling approach to identify, at a relatively low computational cost, stimulation settings potentially associated with a significantly higher degree of efficiency and selectivity compared with stimulation settings determined post-operatively. Our data reinforce the hypothesis that model-based control strategies are crucial for the design of novel stimulation protocols at the backstage of clinical applications.

  17. Algorithmic design of a noise-resistant and efficient closed-loop deep brain stimulation system: A computational approach

    PubMed Central

    Karamintziou, Sofia D.; Custódio, Ana Luísa; Piallat, Brigitte; Polosan, Mircea; Chabardès, Stéphan; Stathis, Pantelis G.; Tagaris, George A.; Sakas, Damianos E.; Polychronaki, Georgia E.; Tsirogiannis, George L.; David, Olivier; Nikita, Konstantina S.

    2017-01-01

    Advances in the field of closed-loop neuromodulation call for analysis and modeling approaches capable of confronting challenges related to the complex neuronal response to stimulation and the presence of strong internal and measurement noise in neural recordings. Here we elaborate on the algorithmic aspects of a noise-resistant closed-loop subthalamic nucleus deep brain stimulation system for advanced Parkinson’s disease and treatment-refractory obsessive-compulsive disorder, ensuring remarkable performance in terms of both efficiency and selectivity of stimulation, as well as in terms of computational speed. First, we propose an efficient method drawn from dynamical systems theory, for the reliable assessment of significant nonlinear coupling between beta and high-frequency subthalamic neuronal activity, as a biomarker for feedback control. Further, we present a model-based strategy through which optimal parameters of stimulation for minimum energy desynchronizing control of neuronal activity are being identified. The strategy integrates stochastic modeling and derivative-free optimization of neural dynamics based on quadratic modeling. On the basis of numerical simulations, we demonstrate the potential of the presented modeling approach to identify, at a relatively low computational cost, stimulation settings potentially associated with a significantly higher degree of efficiency and selectivity compared with stimulation settings determined post-operatively. Our data reinforce the hypothesis that model-based control strategies are crucial for the design of novel stimulation protocols at the backstage of clinical applications. PMID:28222198

  18. Design, Fabrication, Simulation and Characterization of a Novel Dual-Sided Microelectrode Array for Deep Brain Recording and Stimulation

    PubMed Central

    Zhao, Zongya; Gong, Ruxue; Huang, Hongen; Wang, Jue

    2016-01-01

    In this paper, a novel dual-sided microelectrode array is specially designed and fabricated for a rat Parkinson’s disease (PD) model to study the mechanisms of deep brain stimulation (DBS). The fabricated microelectrode array can stimulate the subthalamic nucleus and simultaneously record electrophysiological information from multiple nuclei of the basal ganglia system. The fabricated microelectrode array has a long shaft of 9 mm and each planar surface is equipped with three stimulating sites (diameter of 100 μm), seven electrophysiological recording sites (diameter of 20 μm) and four sites with diameter of 50 μm used for neurotransmitter measurements in future work. The performances of the fabricated microelectrode array were characterized by scanning electron microscopy (SEM), electrochemical impedance spectroscopy (EIS) and cyclic voltammetry. In addition, the stimulating effects of the fabricated microelectrode were evaluated by finite element modeling (FEM). Preliminary animal experiments demonstrated that the designed microelectrode arrays can record spontaneous discharge signals from the striatum, the subthalamic nucleus and the globus pallidus interna. The designed and fabricated microelectrode arrays provide a powerful research tool for studying the mechanisms of DBS in rat PD models. PMID:27314356

  19. Deep Brain Stimulation for Movement Disorders.

    PubMed

    Revell, Maria A

    2015-12-01

    Disruption in the interaction between the central nervous system, nerves, and muscles cause movement disorders. These disorders can negatively affect quality of life. Deep brain stimulation (DBS) has been identified as a therapy for Parkinson disease and essential tremor that has significant advantages compared with medicinal therapies. Surgical intervention for these disorders before DBS included ablative therapies such as thalamotomy and pallidotomy. These procedures were not reversible and did not allow for treatment adjustments. The advent of DBS progressed therapies for significant movement disorders into the realm of being reversible and adjustable based on patient symptoms.

  20. [Deep brain stimulation in psychiatry: ethical aspects].

    PubMed

    Müller, Ulf J; Bogerts, Bernhard; Voges, Jürgen; Galazky, Imke; Kohl, Sina; Heinze, Hans-Jochen; Kuhn, Jens; Steiner, Johann

    2014-07-01

    Deep brain stimulation (DBS) has been shown to be an efficacious treatment for many neurological conditions and has thus been expanded to psychiatric diseases as well. Following an introduction on the history of DBS in psychiatry, this review summarizes commonly raised ethical concerns and questions on clinical trial design, selection of patients, informed consent and concerns about the possible impact of DBS on an individual's personality. Finally, it highlights the fact that critique on DBS in psychiatry is probably not selectively based on scientific concerns about potential risks; instead, the neurobiological origin of specific psychiatric disorders has been questioned.

  1. Deep brain stimulation for movement disorders.

    PubMed

    Thevathasan, Wesley; Gregory, Ralph

    2010-02-01

    Deep brain stimulation is now considered a routine treatment option for selected patients with advanced Parkinson's disease, primary segmental and generalised dystonia, and essential tremor. The neurosurgeon is responsible for the accurate and safe placement of the electrodes and the neurologist for the careful selection of patients and titration of medication against the effects of stimulation. A multidisciplinary team approach involving specialist nurses, neuropsychologists and neurophysiologists is required for a successful outcome. In this article we will summarise the key points in patient selection, provide an overview of the surgical technique, and discuss the beneficial and adverse outcomes that can occur.

  2. Deep brain stimulation for Tourette syndrome.

    PubMed

    Kim, Won; Pouratian, Nader

    2014-01-01

    Gilles de la Tourette syndrome is a movement disorder characterized by repetitive stereotyped motor and phonic movements with varying degrees of psychiatric comorbidity. Deep brain stimulation (DBS) has emerged as a novel therapeutic intervention for patients with refractory Tourette syndrome. Since 1999, more than 100 patients have undergone DBS at various targets within the corticostriatothalamocortical network thought to be implicated in the underlying pathophysiology of Tourette syndrome. Future multicenter clinical trials and the use of a centralized online database to compare the results are necessary to determine the efficacy of DBS for Tourette syndrome. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Use of brain MRI after deep brain stimulation hardware implantation.

    PubMed

    Nazzaro, Jules M; Lyons, Kelly E; Wetzel, Louis H; Pahwa, Rajesh

    2010-03-01

    The objective of this study was to examine the experience with and safety of brain 1.5 Tesla (T) magnetic resonance imaging (MRI) in deep brain stimulation (DBS) patients. This was a retrospective review of brain MRI scanning performed on DBS patients at the University of Kansas Medical Center between January 1995 and December 2007. A total of 249 DBS patients underwent 445 brain 1.5 T MRI scan sessions encompassing 1,092 individual scans using a transmit-receive head coil, representing the cumulative scanning of 1,649 DBS leads. Patients with complete implanted DBS systems as well as those with externalized leads underwent brain imaging. For the majority of scans, specific absorption rates localized to the head (SAR(H)) were estimated and in all cases SAR(H) were higher than that specified in the present product labeling. There were no clinical or hardware related adverse events secondary to brain MRI scanning. Our data should not be extrapolated to encourage MRI scanning beyond the present labeling. Rather, our data may contribute to further defining safe MRI scanning parameters that might ultimately be adopted in future product labeling as more centers report in detail their experiences.

  4. Improved electrode material for deep brain stimulation.

    PubMed

    Petrossians, A; Whalen, J J; Weiland, J D

    2016-08-01

    Deep brain stimulation (DBS) devices have been implanted for treatment of basic tremor, Parkinson's disease and dystonia. These devices use electrodes in contact with tissue to deliver electrical pulses to targeted cells, to elicit specific therapeutic responses. In general, the neuromodulation industry has been evolving towards smaller, less invasive electrodes. However, current electrode materials do not support small sizes without severely restricting the stimulus output. Hence, an improved electrode material will benefit present and future DBS systems. In this study, five DBS leads were modified using a cost-effective and materials-efficient process for applying an ultra-low impedance platinum-iridium alloy coating. One DBS lead was used for insertion test and four DBS leads were chronically pulsed for 12 weeks. The platinum-iridium alloy significantly improved the electrical properties of the DBS electrodes and was robust to insertion into brain and to 12 weeks of chronic pulsing.

  5. Effects of deep brain stimulation and medication on strength, bradykinesia, and electromyographic patterns of the ankle joint in Parkinson's disease.

    PubMed

    Vaillancourt, David E; Prodoehl, Janey; Sturman, Molly M; Bakay, Roy A E; Metman, Leo Verhagen; Corcos, Daniel M

    2006-01-01

    We investigated the control of movement in 12 patients with Parkinson's disease (PD) after they received surgically implanted high-frequency stimulating electrodes in the subthalamic nucleus (STN). The experiment studied ankle strength, movement velocity, and the associated electromyographic patterns in PD patients, six of whom had tremor at the ankle. The patients were studied off treatment, ON STN deep brain stimulation (DBS), on medication, and on medication plus STN DBS. Twelve matched control subjects were also examined. Medication alone and STN DBS alone increased patients' ankle strength, ankle velocity, agonist muscle burst amplitude, and agonist burst duration, while reducing the number of agonist bursts during movement. These findings were similar for PD patients with and without tremor. The combination of medication plus STN DBS normalized maximal strength at the ankle joint, but ankle movement velocity and electromyographic patterns were not normalized. The findings are the first to demonstrate that STN DBS and medication increase strength and movement velocity at the ankle joint.

  6. COMMUNICATION: Toward closed-loop optimization of deep brain stimulation for Parkinson's disease: concepts and lessons from a computational model

    NASA Astrophysics Data System (ADS)

    Feng, Xiao-jiang; Greenwald, Brian; Rabitz, Herschel; Shea-Brown, Eric; Kosut, Robert

    2007-06-01

    Deep brain stimulation (DBS) of the subthalamic nucleus with periodic, high-frequency pulse trains is an increasingly standard therapy for advanced Parkinson's disease. Here, we propose that a closed-loop global optimization algorithm may identify novel DBS waveforms that could be more effective than their high-frequency counterparts. We use results from a computational model of the Parkinsonian basal ganglia to illustrate general issues relevant to eventual clinical or experimental tests of such an algorithm. Specifically, while the relationship between DBS characteristics and performance is highly complex, global search methods appear able to identify novel and effective waveforms with convergence rates that are acceptably fast to merit further investigation in laboratory or clinical settings.

  7. Deep brain stimulation or thalamotomy in fragile X-associated tremor/ataxia syndrome? Case report.

    PubMed

    Tamás, Gertrúd; Kovács, Norbert; Varga, Noémi Ágnes; Barsi, Péter; Erőss, Loránd; Molnár, Mária Judit; Balás, István

    2016-01-01

    We present the case of a 66-year-old man who has been treated for essential tremor since the age of 58. He developed mild cerebellar gait ataxia seven years after tremor onset. Moderate, global brain atrophy was identified on MRI scans. At the age of 68, only temporary tremor relief could be achieved by bilateral deep brain stimulation of the ventral intermedius nucleus of the thalamus. Bilateral stimulation of the subthalamic nucleus also resulted only in transient improvement. In the meantime, progressive gait ataxia and tetraataxia developed accompanied by other cerebellar symptoms, such as nystagmus and scanning speech. These correlated with progressive development of bilateral symmetric hyperintensity of the middle cerebellar peduncles on T2 weighted MRI scans. Genetic testing revealed premutation of the FMR1 gene, establishing the diagnosis of fragile X-associated tremor/ataxia syndrome. Although this is a rare disorder, it should be taken into consideration during preoperative evaluation of essential tremor. Postural tremor ceased two years later after thalamotomy on the left side, while kinetic tremor of the right hand also improved. Copyright © 2016 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  8. Current Steering to Control the Volume of Tissue Activated During Deep Brain Stimulation

    PubMed Central

    Butson, Christopher R.; McIntyre, Cameron C.

    2009-01-01

    Background Over the last two decades, deep brain stimulation (DBS) has become a recognized and effective clinical therapy for numerous neurological conditions. Since its inception, clinical DBS technology has progressed at a relatively slow rate; however, advances in neural engineering research have the potential to improve DBS systems. One such advance is the concept of current steering, or the use of multiple stimulation sources to direct current flow through targeted regions of brain tissue. Objective The goals of this study were to develop a theoretical understanding of the effects of current steering in the context of DBS, and use that information to evaluate the potential utility of current steering during stimulation of the subthalamic nucleus. Methods We used finite element electric field models, coupled to multi-compartment cable axon models, to predict the volume of tissue activated (VTA) by DBS as a function of the stimulation parameter settings. Results Balancing current flow through adjacent cathodes increased the VTA magnitude, relative to monopolar stimulation, and current steering enabled us to sculpt the shape of the VTA to fit a given anatomical target. Conclusions These results provide motivation for the integration of current steering technology into clinical DBS systems, thereby expanding opportunities to customize DBS to individual patients, and potentially enhancing therapeutic efficacy. PMID:19142235

  9. Ethical safety of deep brain stimulation: A study on moral decision-making in Parkinson's disease.

    PubMed

    Fumagalli, Manuela; Marceglia, Sara; Cogiamanian, Filippo; Ardolino, Gianluca; Picascia, Marta; Barbieri, Sergio; Pravettoni, Gabriella; Pacchetti, Claudio; Priori, Alberto

    2015-07-01

    The possibility that deep brain stimulation (DBS) in Parkinson's disease (PD) alters patients' decisions and actions, even temporarily, raises important clinical, ethical and legal questions. Abnormal moral decision-making can lead to ethical rules violations. Previous experiments demonstrated the subthalamic (STN) activation during moral decision-making. Here we aim to study whether STN DBS can affect moral decision-making in PD patients. Eleven patients with PD and bilateral STN DBS implant performed a computerized moral task in ON and OFF stimulation conditions. A control group of PD patients without DBS implant performed the same experimental protocol. All patients underwent motor, cognitive and psychological assessments. STN stimulation was not able to modify neither reaction times nor responses to moral task both when we compared the ON and the OFF state in the same patient (reaction times, p = .416) and when we compared DBS patients with those treated only with the best medical treatment (reaction times: p = .408, responses: p = .776). Moral judgment is the result of a complex process, requiring cognitive executive functions, problem-solving, anticipations of consequences of an action, conflict processing, emotional evaluation of context and of possible outcomes, and involving different brain areas and neural circuits. Our data show that STN DBS leaves unaffected moral decisions thus implying relevant clinical and ethical implications for DBS consequences on patients' behavior, on decision-making and on judgment ability. In conclusion, the technique can be considered safe on moral behavior. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Subthalamic Nucleus Stimulation Modulates Thalamic Neuronal Activity

    PubMed Central

    Xu, Weidong; Russo, Gary S.; Hashimoto, Takao; Zhang, Jianyu; Vitek, Jerrold L.

    2009-01-01

    Deep brain stimulation (DBS) in the subthalamic nucleus (STN) is an effective tool for the treatment of advanced Parkinson’s disease. The mechanism by which STN DBS elicits its beneficial effect, however, remains unclear. We previously reported STN stimulation increased the rate and produced a more regular and periodic pattern of neuronal activity in the internal segment of the globus pallidus (GPi). Here we extend our observations to neurons in the pallidal (ventralis lateralis pars oralis (VLo) and ventralis anterior (VA)) and cerebellar (ventralis lateralis posterior pars oralis (VPLo)) receiving areas of the motor thalamus during STN DBS. Stimulation parameters that produced improvement in rigidity and bradykinesia resulted in changes in the pattern and power of oscillatory activity of neuronal activity that were similar in both regions of the motor thalamus. Neurons in both VA/VLo and VPLo tended to become more periodic and regular with a shift in oscillatory activity from low to high frequencies. Burst activity was reduced in VA/VLo, but was not significantly changed in VPLo. There was also a significant shift in the population of VA/VLo neurons that were inhibited during STN DBS, while VPLo neurons tended to be activated. These data are consistent with the hypothesis that STN DBS increases output from the nucleus and produces a change in the pattern and periodicity of neuronal activity in the basal ganglia thalamic network, and that these changes include cerebellar pathways likely via activation of adjacent cerebello-thalamic fiber bundles. PMID:19005057

  11. The ethics of deep brain stimulation (DBS).

    PubMed

    Unterrainer, Marcus; Oduncu, Fuat S

    2015-11-01

    Deep brain stimulation (DBS) is an invasive technique designed to stimulate certain deep brain regions for therapeutic purposes and is currently used mainly in patients with neurodegenerative disorders, such as Parkinson's disease. However, DBS is also used increasingly for other experimental applications, such as the treatment of psychiatric disorders (e.g. severe depression), weight reduction. Apart from its therapeutic potential, DBS can cause severe adverse effects, some that might also have a significant impact on the patient's personality and autonomy by the external stimulation of DBS which effects lie beyond the individual's control and free will. The article's purpose is to outline the procedures of DBS currently used in therapeutic and experimental applications and to discuss the ethical concerns regarding this procedure. It will address the clinical benefit-risk-ratio, the particular ethics of research in this field, and the ethical issues raised by affecting a patient's or an individual's personality and autonomous behaviour. Moreover, a potential ethical guideline, the Ulysses contract is discussed for the field of clinical application as well as the question of responsibility.

  12. Origin and Evolution of Deep Brain Stimulation

    PubMed Central

    Sironi, Vittorio A.

    2011-01-01

    This paper briefly describes how the electrical stimulation, used since antiquity to modulate the nervous system, has been a fundamental tool of neurophysiologic investigation in the second half of the eighteenth century and was subsequently used by the early twentieth century, even for therapeutic purposes. In mid-twentieth century the advent of stereotactic procedures has allowed the drift from lesional to stimulating technique of deep nuclei of the brain for therapeutic purposes. In this way, deep brain stimulation (DBS) was born, that, over the last two decades, has led to positive results for the treatment of medically refractory Parkinson’s disease, essential tremor, and dystonia. In recent years, the indications for therapeutic use of DBS have been extended to epilepsy, Tourette’s syndrome, psychiatric diseases (depression, obsessive–compulsive disorder), some kinds of headache, eating disorders, and the minimally conscious state. The potentials of the DBS for therapeutic use are fascinating, but there are still many unresolved technical and ethical problems, concerning the identification of the targets for each disease, the selection of the patients and the evaluation of the results. PMID:21887135

  13. Deep Brain Stimulation, Authenticity and Value.

    PubMed

    Pugh, Jonathan; Maslen, Hannah; Savulescu, Julian

    2017-10-01

    Deep brain stimulation has been of considerable interest to bioethicists, in large part because of the effects that the intervention can occasionally have on central features of the recipient's personality. These effects raise questions regarding the philosophical concept of authenticity. In this article, we expand on our earlier work on the concept of authenticity in the context of deep brain stimulation by developing a diachronic, value-based account of authenticity. Our account draws on both existentialist and essentialist approaches to authenticity, and Laura Waddell Ekstrom's coherentist approach to personal autonomy. In developing our account, we respond to Sven Nyholm and Elizabeth O'Neill's synchronic approach to authenticity, and explain how the diachronic approach we defend can have practical utility, contrary to Alexandre Erler and Tony Hope's criticism of autonomy-based approaches to authenticity. Having drawn a distinction between the authenticity of an individual's traits and the authenticity of that person's values, we consider how our conception of authenticity applies to the context of anorexia nervosa in comparison to other prominent accounts of authenticity. We conclude with some reflections on the prudential value of authenticity, and by highlighting how the language of authenticity can be invoked to justify covert forms of paternalism that run contrary to the value of individuality that seems to be at the heart of authenticity.

  14. Subthalamic nucleus stimulation reverses mediofrontal influence over decision threshold.

    PubMed

    Cavanagh, James F; Wiecki, Thomas V; Cohen, Michael X; Figueroa, Christina M; Samanta, Johan; Sherman, Scott J; Frank, Michael J

    2011-09-25

    It takes effort and time to tame one's impulses. Although medial prefrontal cortex (mPFC) is broadly implicated in effortful control over behavior, the subthalamic nucleus (STN) is specifically thought to contribute by acting as a brake on cortico-striatal function during decision conflict, buying time until the right decision can be made. Using the drift diffusion model of decision making, we found that trial-to-trial increases in mPFC activity (EEG theta power, 4-8 Hz) were related to an increased threshold for evidence accumulation (decision threshold) as a function of conflict. Deep brain stimulation of the STN in individuals with Parkinson's disease reversed this relationship, resulting in impulsive choice. In addition, intracranial recordings of the STN area revealed increased activity (2.5-5 Hz) during these same high-conflict decisions. Activity in these slow frequency bands may reflect a neural substrate for cortico-basal ganglia communication regulating decision processes.

  15. Neuronal activity in the human subthalamic nucleus encodes decision conflict during action selection

    PubMed Central

    Zaghloul, Kareem A.; Weidemann, Christoph T.; Lega, Bradley C.; Jaggi, Jurg L.; Baltuch, Gordon H.; Kahana, Michael J.

    2012-01-01

    The subthalamic nucleus (STN), which receives excitatory inputs from the cortex and has direct connections with the inhibitory pathways of the basal ganglia, is well positioned to efficiently mediate action selection. Here, we use microelectrode recordings captured during deep brain stimulation surgery as participants engage in a decision task to examine the role of the human STN in action selection. We demonstrate that spiking activity in the STN increases when participants engage in a decision, and that the level of spiking activity increases with the degree of decision conflict. These data implicate the STN as an important mediator of action selection during decision processes. PMID:22396419

  16. Combined pallidal and subthalamic nucleus stimulation in sporadic dystonia-parkinsonism.

    PubMed

    Wöhrle, Johannes C; Blahak, Christian; Capelle, Hans-Holger; Fogel, Wolfgang; Bäzner, Hansjoerg; Krauss, Joachim K

    2012-01-01

    Multifocal deep brain stimulation (DBS) is a new technique that has been introduced recently. A 39-year-old man with dystonia-parkinsonism underwent the simultaneous implantation of subthalamic nucleus (STN) and globus pallidus internus (GPi) DBS electrodes. While bilateral STN DBS controlled the parkinsonian symptoms well and allowed for a reduction in levodopa, the improvement of dystonia was only temporary. Additional GPi DBS also alleviated dystonic symptoms. Formal assessment at the 1-year follow-up showed that both the parkinsonian symptoms and the dystonia were markedly improved via continuous bilateral combined STN and GPi stimulation. Sustained benefit was achieved at 3 years postoperatively.

  17. Processing of emotional information in the human subthalamic nucleus.

    PubMed

    Buot, Anne; Welter, Marie-Laure; Karachi, Carine; Pochon, Jean-Baptiste; Bardinet, Eric; Yelnik, Jérôme; Mallet, Luc

    2013-12-01

    The subthalamic nucleus (STN) is an efficient target for treating patients with Parkinson's disease as well as patients with obsessive-compulsive disorder (OCD) using high frequency stimulation (HFS). In both Parkinson's disease and OCD patients, STN-HFS can trigger abnormal behaviours, such as hypomania and impulsivity. To investigate if this structure processes emotional information, and whether it depends on motor demands, we recorded subthalamic local field potentials in 16 patients with Parkinson's disease using deep brain stimulation electrodes. Recordings were made with and without dopaminergic treatment while patients performed an emotional categorisation paradigm in which the response varied according to stimulus valence (pleasant, unpleasant and neutral) and to the instruction given (motor, non-motor and passive). Pleasant, unpleasant and neutral stimuli evoked an event related potential (ERP). Without dopamine medication, ERP amplitudes were significantly larger for unpleasant compared with neutral pictures, whatever the response triggered by the stimuli; and the magnitude of this effect was maximal in the ventral part of the STN. No significant difference in ERP amplitude was observed for pleasant pictures. With dopamine medication, ERP amplitudes were significantly increased for pleasant compared with neutral pictures whatever the response triggered by the stimuli, while ERP amplitudes to unpleasant pictures were not modified. These results demonstrate that the ventral part of the STN processes the emotional valence of stimuli independently of the motor context and that dopamine enhances processing of pleasant information. These findings confirm the specific involvement of the STN in emotional processes in human, which may underlie the behavioural changes observed in patients with deep brain stimulation.

  18. Embedded Ultrathin Cluster Electrodes for Long-Term Recordings in Deep Brain Centers

    PubMed Central

    Thorbergsson, Palmi Thor; Ekstrand, Joakim; Friberg, Annika; Granmo, Marcus; Pettersson, Lina M. E.; Schouenborg, Jens

    2016-01-01

    Neural interfaces which allow long-term recordings in deep brain structures in awake freely moving animals have the potential of becoming highly valuable tools in neuroscience. However, the recording quality usually deteriorates over time, probably at least partly due to tissue reactions caused by injuries during implantation, and subsequently micro-forces due to a lack of mechanical compliance between the tissue and neural interface. To address this challenge, we developed a gelatin embedded neural interface comprising highly flexible electrodes and evaluated its long term recording properties. Bundles of ultrathin parylene C coated platinum electrodes (N = 29) were embedded in a hard gelatin based matrix shaped like a needle, and coated with Kollicoat™ to retard dissolution of gelatin during the implantation. The implantation parameters were established in an in vitro model of the brain (0.5% agarose). Following a craniotomy in the anesthetized rat, the gelatin embedded electrodes were stereotactically inserted to a pre-target position, and after gelatin dissolution the electrodes were further advanced and spread out in the area of the subthalamic nucleus (STN). The performance of the implanted electrodes was evaluated under anesthesia, during 8 weeks. Apart from an increase in the median-noise level during the first 4 weeks, the electrode impedance and signal-to-noise ratio of single-units remained stable throughout the experiment. Histological postmortem analysis confirmed implantation in the area of STN in most animals. In conclusion, by combining novel biocompatible implantation techniques and ultra-flexible electrodes, long-term neuronal recordings from deep brain structures with no significant deterioration of electrode function were achieved. PMID:27159159

  19. Deep Brain Electrical Stimulation in Epilepsy

    NASA Astrophysics Data System (ADS)

    Rocha, Luisa L.

    2008-11-01

    The deep brain electrical stimulation has been used for the treatment of neurological disorders such as Parkinson's disease, chronic pain, depression and epilepsy. Studies carried out in human brain indicate that the application of high frequency electrical stimulation (HFS) at 130 Hz in limbic structures of patients with intractable temporal lobe epilepsy abolished clinical seizures and significantly decreased the number of interictal spikes at focus. The anticonvulsant effects of HFS seem to be more effective in patients with less severe epilepsy, an effect associated with a high GABA tissue content and a low rate of cell loss. In addition, experiments using models of epilepsy indicate that HFS (pulses of 60 μs width at 130 Hz at subthreshold current intensity) of specific brain areas avoids the acquisition of generalized seizures and enhances the postictal seizure suppression. HFS is also able to modify the status epilepticus. It is concluded that the effects of HFS may be a good strategy to reduce or avoid the epileptic activity.

  20. Chronic stress-like syndrome as a consequence of medial site subthalamic stimulation in Parkinson's disease.

    PubMed

    Růžička, Filip; Jech, Robert; Nováková, Lucie; Urgošík, Dušan; Bezdíček, Ondřej; Vymazal, Josef; Růžička, Evžen

    2015-02-01

    Considering the functional organization of the subthalamic nucleus (STN), we hypothesized that subthalamic deep brain stimulation (STN-DBS) in Parkinson's disease might have a differential impact on the hypothalamic-pituitary-adrenal axis in relation to the position of active stimulating contact within the STN. In addition, we searched for any STN-DBS-related morning plasma cortisol changes in association with postoperative anxiety and weight gain. A plasma cortisol measurement was performed on the day of initiation of bilateral STN-DBS and repeated after 1 and 17 months in twenty patients with advanced Parkinson's disease. The body weight change and anxiety scores following the implantation were assessed as well. The electrode positions in the STN were determined on T1-weighted magnetic resonance images. After initiation of stimulation, cortisol levels significantly decreased and the cortisol changes after 1 and 17 months strongly correlated with the position of active contact in the subthalamic area. Patients with at least one contact located more medially in the STN experienced a significantly greater decrease of cortisol than those with one or both active contacts more laterally. Furthermore, the lower cortisol levels were strongly associated with higher trait anxiety and weight gain. These changes mimicked the effects of chronic stress and suggest the disturbing impact of STN-DBS on limbic and motivational systems.

  1. Comparison of weight gain and energy intake after subthalamic versus pallidal stimulation in Parkinson's disease.

    PubMed

    Sauleau, Paul; Leray, Emmanuelle; Rouaud, Tiphaine; Drapier, Sophie; Drapier, Dominique; Blanchard, Sophie; Drillet, Gwenolla; Péron, Julie; Vérin, Marc

    2009-10-30

    To compare body mass index (BMI) and daily energy intake (DEI) after subthalamic versus pallidal deep brain stimulation (DBS). Weight gain following DBS in Parkinson's disease patients remains largely unexplained and no comparison of subthalamic and pallidal (GPi) stimulation has yet been performed. BMI and DEI, dopaminergic drug administration and motor scores were recorded in 46 patients with PD before STN (n = 32) or GPi (n = 14) DBS and 3 and 6 months after. At M6, BMI had increased by an average of 8.4% in the STN group and 3.2% in the GPi group. BMI increased in 28 STN and 9 GPi patients. This increase was significantly higher in the STN group (P < 0.048) and the difference remained significant after adjustment for reduced dopaminergic medication; 28.6% of GPi patients were overweight at 6 months (14.3% preoperatively) versus 37.5% of STN patients (21.9% preoperatively). Changes in BMI were negatively correlated with changes in dyskinesia in the GPi-DBS group. Food intake did not change in the two groups, either quantitatively or qualitatively. Frequent weight gain, inadequately explained by motor improvement or reduced dopaminergic drug dosage, occurred in subthalamic DBS patients. The difference between groups suggests additional factors in the STN group, such as homeostatic control center involvement.

  2. Modulation of the cerebello-thalamo-cortical network in thalamic deep brain stimulation for tremor: a diffusion tensor imaging study.

    PubMed

    Coenen, Volker A; Allert, Niels; Paus, Sebastian; Kronenbürger, Martin; Urbach, Horst; Mädler, Burkhard

    2014-12-01

    Deep brain stimulation alleviates tremor of various origins. Several regions like the ventralis intermediate nucleus of thalamus, the caudal zona incerta, and the posterior subthalamic region are generally targeted. Previous work with fiber tractography has shown the involvement of the cerebello-thalamo-cortical network in tremor control. To report the results of a prospective trial in a group of patients with tremor who underwent post hoc tractographic analysis after treatment with traditional thalamic deep brain stimulation. A total of 11 patients (aged 64 ± 17 years, 6 male) were enrolled (essential tremor [6], Parkinson tremor [3], and myoclonic tremor in myoclonus dystonia [2]). Patients received 1 (3 patients), 2 (7 patients), or 3 (1 patient) quadripolar electrodes. A 32-direction diffusion tensor magnetic resonance imaging sequence was acquired preoperatively. Tractography was processed postoperatively for evaluation and the dentato-rubro-thalamic tract (DRT) was individually tracked. Electrode positions were determined with helical computed tomography. Electric fields (EFs) were simulated according to individual stimulation parameters in a standardized atlas brain space (ICBM-MNI 152). Tremor was reduced in all patients (69.4% mean) on the global (bilateral) tremor score. Effective contacts were located inside or in proximity to the DRT. In moderate tremor reduction (2 patients), the EFs were centered on its anterior border. In good and excellent tremor reduction (9 patients), EFs focused on its center. Deep brain stimulation of the cerebello-thalamo-cortical network reduces tremor. The DRT connects 3 traditional target regions for deep brain stimulation in tremor disease. Tractography techniques can be used to directly visualize the DRT and, therefore, optimize target definition in individual patients.

  3. Deep brain stimulation: from neurology to psychiatry?

    PubMed

    Krack, Paul; Hariz, Marwan I; Baunez, Christelle; Guridi, Jorge; Obeso, Jose A

    2010-10-01

    Functional stereotaxy was introduced in the late 1940s to reduce the morbidity of lobotomy in psychiatric disease by using more focal lesions. The advent of neuroleptics led to a drastic decline in psychosurgery for several decades. Functional stereotactic neurosurgery has recently been revitalized, starting with treatment of Parkinson's disease, in which deep brain stimulation (DBS) facilitates reversible focal neuromodulation of altered basal ganglia circuits. DBS is now being extended to treatment of neuropsychiatric conditions such as Gilles de la Tourette syndrome, obsessive-compulsive disorder, depression and addiction. In this review, we discuss the concept that dysfunction of motor, limbic and associative cortico-basal ganglia-thalamocortical loops underlies these various disorders, which might now be amenable to DBS treatment. Copyright © 2010 Elsevier Ltd. All rights reserved.

  4. Deep brain stimulation to reduce sexual drive

    PubMed Central

    Fuss, Johannes; Auer, Matthias K.; Biedermann, Sarah V.; Briken, Peer; Hacke, Werner

    2015-01-01

    To date there are few treatment options to reduce high sexual drive or sexual urges in paraphilic patients with a risk for sexual offending. Pharmacological therapy aims to reduce sexual drive by lowering testosterone at the cost of severe side effects. We hypothesize that high sexual drive could also be reduced with deep brain stimulation (DBS) of circuits that generate sexual drive. This approach would help to avoid systemic side effects of antiandrogenic drug therapies. So far the best investigated target to reduce sexual drive is the ventromedial hypothalamus, which was lesioned unilaterally and bilaterally by stereotaxic interventions in paraphilic patients in the 1970s. Here, we discuss DBS as a treatment strategy in patients with severe paraphilic disorders with a serious risk of sexual offending. There are profound ethical and practical issues associated with DBS treatment of paraphilic patients that must be solved before considering such a treatment approach. PMID:26057198

  5. Deep Brain Stimulation for Psychiatric Disorders

    PubMed Central

    Holtzheimer, Paul E.; Mayberg, Helen S.

    2015-01-01

    Medications, psychotherapy, and other treatments are effective for many patients with psychiatric disorders. However, with currently available interventions, a substantial number of patients experience incomplete resolution of symptoms, and relapse rates are high. In the search for better treatments, increasing interest has focused on focal neuromodulation. This focus has been driven by improved neuroanatomical models of mood, thought, and behavior regulation, as well as by more advanced strategies for directly and focally altering neural activity. Deep brain stimulation (DBS) is one of the most invasive focal neuromodulation techniques available; data have supported its safety and efficacy in a number of movement disorders. Investigators have produced preliminary data on the safety and efficacy of DBS for several psychiatric disorders, as well. In this review, we describe the development and justification for testing DBS for various psychiatric disorders, carefully consider the available clinical data, and briefly discuss potential mechanisms of action. PMID:21692660

  6. Analysis of electrodes' placement and deformation in deep brain stimulation from medical images

    NASA Astrophysics Data System (ADS)

    Mehri, Maroua; Lalys, Florent; Maumet, Camille; Haegelen, Claire; Jannin, Pierre

    2012-02-01

    Deep brain stimulation (DBS) is used to reduce the motor symptoms such as rigidity or bradykinesia, in patients with Parkinson's disease (PD). The Subthalamic Nucleus (STN) has emerged as prime target of DBS in idiopathic PD. However, DBS surgery is a difficult procedure requiring the exact positioning of electrodes in the pre-operative selected targets. This positioning is usually planned using patients' pre-operative images, along with digital atlases, assuming that electrode's trajectory is linear. However, it has been demonstrated that anatomical brain deformations induce electrode's deformations resulting in errors in the intra-operative targeting stage. In order to meet the need of a higher degree of placement accuracy and to help constructing a computer-aided-placement tool, we studied the electrodes' deformation in regards to patients' clinical data (i.e., sex, mean PD duration and brain atrophy index). Firstly, we presented an automatic algorithm for the segmentation of electrode's axis from post-operative CT images, which aims to localize the electrodes' stimulated contacts. To assess our method, we applied our algorithm on 25 patients who had undergone bilateral STNDBS. We found a placement error of 0.91+/-0.38 mm. Then, from the segmented axis, we quantitatively analyzed the electrodes' curvature and correlated it with patients' clinical data. We found a positive significant correlation between mean curvature index of the electrode and brain atrophy index for male patients and between mean curvature index of the electrode and mean PD duration for female patients. These results help understanding DBS electrode' deformations and would help ensuring better anticipation of electrodes' placement.

  7. Deep-brain stimulation for anorexia nervosa.

    PubMed

    Wu, Hemmings; Van Dyck-Lippens, Pieter Jan; Santegoeds, Remco; van Kuyck, Kris; Gabriëls, Loes; Lin, Guozhen; Pan, Guihua; Li, Yongchao; Li, Dianyou; Zhan, Shikun; Sun, Bomin; Nuttin, Bart

    2013-01-01

    Anorexia nervosa (AN) is a complex and severe, sometimes life-threatening, psychiatric disorder with high relapse rates under standard treatment. After decades of brain-lesioning procedures offered as a last resort, deep-brain stimulation (DBS) has come under investigation in the last few years as a treatment option for severe and refractory AN. In this jointly written article, Sun et al. (the Shanghai group) report an average of 65% increase in body weight in four severe and refractory patients with AN after they underwent the DBS procedure (average follow-up: 38 months). All patients weighed greater than 85% of expected body weight and thus no longer met the diagnostic criteria of AN at last follow-up. Nuttin et al. (the Leuven group) describe other clinical studies that provide evidence for the use of DBS for AN and further discuss patient selection criteria, target selection, and adverse event of this evolving therapy. Preliminary results from the Shanghai group and other clinical centers showed that the use of DBS to treat AN may be a valuable option for weight restoration in otherwise-refractory and life-threatening cases. The nature of this procedure, however, remains investigational and should not be viewed as a standard clinical treatment option. Further scientific investigation is essential to warrant the long-term efficacy and safety of DBS for AN. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Deep brain stimulation for chronic pain.

    PubMed

    Boccard, Sandra G J; Pereira, Erlick A C; Aziz, Tipu Z

    2015-10-01

    Deep brain stimulation (DBS) is a neurosurgical intervention popularised in movement disorders such as Parkinson's disease, and also reported to improve symptoms of epilepsy, Tourette's syndrome, obsessive compulsive disorders and cluster headache. Since the 1950s, DBS has been used as a treatment to relieve intractable pain of several aetiologies including post stroke pain, phantom limb pain, facial pain and brachial plexus avulsion. Several patient series have shown benefits in stimulating various brain areas, including the sensory thalamus (ventral posterior lateral and medial), the periaqueductal and periventricular grey, or, more recently, the anterior cingulate cortex. However, this technique remains "off label" in the USA as it does not have Federal Drug Administration approval. Consequently, only a small number of surgeons report DBS for pain using current technology and techniques and few regions approve it. Randomised, blinded and controlled clinical trials that may use novel trial methodologies are desirable to evaluate the efficacy of DBS in patients who are refractory to other therapies. New imaging techniques, including tractography, may help optimise electrode placement and clinical outcome.

  9. Computational analysis of deep brain stimulation.

    PubMed

    McIntyre, Cameron C; Miocinovic, Svjetlana; Butson, Christopher R

    2007-09-01

    Chronic, high-frequency electrical stimulation of subcortical brain structures (deep brain stimulation [DBS]) is an effective clinical treatment for several medically refractory neurological disorders. However, the clinical successes of DBS are tempered by the limited understanding of the response of neurons to applied electric fields and scientific definition of the therapeutic mechanisms of DBS remains elusive. In addition, it is presently unclear which electrode designs and stimulation parameters are optimal for maximum therapeutic benefit and minimal side effects. Detailed computer modeling of DBS has recently emerged as a powerful technique to enhance our understanding of the effects of DBS and to create a virtual testing ground for new stimulation paradigms. This review summarizes the fundamentals of neurostimulation modeling and provides an overview of some of the scientific contributions of computer models to the field of DBS. We then provide a prospective view on the application of DBS-modeling tools to augment the clinical utility of DBS and to design the next generation of DBS technology.

  10. Cost of deep brain stimulation for the treatment of Parkinson's disease by surgical stimulation sites.

    PubMed

    Stroupe, Kevin T; Weaver, Frances M; Cao, Lishan; Ippolito, Dolores; Barton, Brandon R; Burnett-Zeigler, Inger E; Holloway, Robert G; Vickrey, Barbara G; Simuni, Tanya; Follett, Kenneth A

    2014-11-01

    To assess costs and effectiveness of deep brain stimulation (DBS) of the internal globus pallidum (GPi) versus subthalamic nucleus (STN) from the provider and societal perspectives for Parkinson's disease (PD) patients in a multicenter randomized trial. All costs from randomization to 36 months were included. Costs were from Department of Veterans Affairs (VA) and Medicare databases and clinical trial data. Quality adjusted life years (QALYs) were from Quality of Well Being questionnaires. Provider costs were similar for the 144 GPi and 130 STN patients (GPi: $138,044 vs. STN: $131,822; difference = $6,222, 95% confidence interval [CI]: -$42,125 to $45,343). Societal costs were also similar (GPi: $171,061 vs. STN: $167,706; difference = $3,356, 95% CI: -$57,371 to $60,294). The GPi patients had nonsignificantly more QALYs. The QALYs and costs were similar; the level of uncertainty given the sample size suggests that these factors should not direct treatment or resource allocation decisions in selecting or making available either procedure for eligible PD patients. © 2014 International Parkinson and Movement Disorder Society.

  11. Deep Brain Stimulation and Cognitive Decline in Parkinson’s Disease: A Clinical Review

    PubMed Central

    Massano, João; Garrett, Carolina

    2012-01-01

    Parkinson’s disease is a common and often debilitating disorder, with a growing prevalence accompanying global population aging. Current drug therapy is not satisfactory enough for many patients, especially after a few years of symptom progression. This is mainly due to the motor complications that frequently emerge as disease progresses. Deep brain stimulation (DBS) is a useful therapeutic option in carefully selected patients that significantly improves motor symptoms, functional status, and quality of life. However, cognitive impairment may limit patient selection for DBS, as patients need to have sufficient mental capabilities in order to understand the procedure, as well as its benefits and limitations, and cooperate with the medical team throughout the process of selection, surgery, and postsurgical follow-up. On the other hand it has been observed that certain aspects of cognitive performance may decline after DBS, namely when the therapeutic target is the widely used subthalamic nucleus. These are important pieces of information for patients, their families, and health care professionals. This manuscript reviews these aspects and their clinical implications. PMID:22557991

  12. Experience with "Fast track" postoperative care after deep brain stimulation surgery.

    PubMed

    Martín, Nuria; Valero, Ricard; Hurtado, Paola; Gracia, Isabel; Fernández, Carla; Rumià, Jordi; Valldeoriola, Francesc; Carrero, Enrique J; Tercero, Francisco Javier; de Riva, Nicolás; Fàbregas, Neus

    A 24-h-stay in the post-anesthesia care unit (PACU) is a common postoperative procedure after deep brain stimulation surgery (DBS). We evaluated the impact of a fast-track (FT) postoperative care protocol. An analysis was performed on all patients who underwent DBS in 2 periods: 2006, overnight monitored care (OMC group), and 2007-2013, FT care (FT group). The study included 19 patients in OMC and 95 patients in FT. Intraoperative complications occurred in 26.3% patients in OMC vs. 35.8% in FT. Post-operatively, one patient in OMC developed hemiparesis, and agitation in 2 patients. In FT, two patients with intraoperative hemiparesis were transferred to the ICU. While on the ward, 3 patients from the FT developed hemiparesis, two of them 48h after the procedure. Thirty eight percent of FT had an MRI scan, while the remaining 62% and all patients of OMC had a CT-scan performed on their transfer to the ward. One patient in OMC had a subthalamic hematoma. Two patients in FT had a pallidal hematoma, and 3 a bleeding along the electrode. A FT discharge protocol is a safe postoperative care after DBS. There are a small percentage of complications after DBS, which mainly occur within the first 6h. Copyright © 2016 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.

  13. Influence of heterogeneous and anisotropic tissue conductivity on electric field distribution in deep brain stimulation.

    PubMed

    Aström, Mattias; Lemaire, Jean-Jacques; Wårdell, Karin

    2012-01-01

    The aim was to quantify the influence of heterogeneous isotropic and heterogeneous anisotropic tissue on the spatial distribution of the electric field during deep brain stimulation (DBS). Three finite element tissue models were created of one patient treated with DBS. Tissue conductivity was modelled as (I) homogeneous isotropic, (II) heterogeneous isotropic based on MRI, and (III) heterogeneous anisotropic based on diffusion tensor MRI. Modelled DBS electrodes were positioned in the subthalamic area, the pallidum, and the internal capsule in each tissue model. Electric fields generated during DBS were simulated for each model and target-combination and visualized with isolevels at 0.20 (inner), and 0.05 V mm(-1) (outer). Statistical and vector analysis was used for evaluation of the distribution of the electric field. Heterogeneous isotropic tissue altered the spatial distribution of the electric field by up to 4% at inner, and up to 10% at outer isolevel. Heterogeneous anisotropic tissue influenced the distribution of the electric field by up to 18 and 15% at each isolevel, respectively. The influence of heterogeneous and anisotropic tissue on the electric field may be clinically relevant in anatomic regions that are functionally subdivided and surrounded by multiple fibres of passage.

  14. Cerebral venous infarction: a potentially avoidable complication of deep brain stimulation surgery.

    PubMed

    Morishita, Takashi; Okun, Michael S; Burdick, Adam; Jacobson, Charles E; Foote, Kelly D

    2013-01-01

    Despite numerous reports on the morbidity and mortality of deep brain stimulation (DBS), cerebral venous infarction has rarely been reported. We present four cases of venous infarct secondary to DBS surgery. The diagnosis of venous infarction was based on 1) delayed onset of new neurologic deficits on postoperative day 1 or 2; 2) significant edema surrounding the superficial aspect of the implanted lead, with or without subcortical hemorrhage on CT scan. Four cases (0.8% per lead, 1.3% per patient) of symptomatic cerebral venous infarction were identified out of 500 DBS lead implantation procedures between July 2002 and August 2009. All four patients had Parkinson's disease. Their DBS leads were implanted in the subthalamic nucleus (n = 2), and the globus pallidus internus (n = 2). Retrospective review of the targeting confirmed that the planned trajectory passed within 3 mm of a cortical vein in two cases for which contrast-enhanced preoperative magnetic resonance (MR) imaging was available. In the other two cases, contrasted targeting images were not obtained preoperatively. Cerebral venous infarction is a potentially avoidable, but serious complication. To minimize its incidence, we propose the use of high-resolution, contrast-enhanced, T1-weighted MR images to delineate cerebral venous anatomy, along with careful stereotactic planning of the lead trajectory to avoid injury to venous structures. © 2013 International Neuromodulation Society.

  15. Swallowing and deep brain stimulation in Parkinson’s disease: A systematic review

    PubMed Central

    Troche, Michelle S.; Brandimore, Alexandra E.; Foote, Kelly D.; Okun, Michael S.

    2013-01-01

    The purpose of this review is to assess the current state of the literature on the topic of deep brain stimulation (DBS) and its effects on swallowing function in Parkinson’s disease (PD). Pubmed, Cochrane review, and web of science searches were completed on all articles addressing DBS that contained a swallowing outcome measure. Outcome measures included the penetration/aspiration scale, pharyngeal transit time, oropharyngeal residue, drooling, aspiration pneumonia, death, hyolaryngeal excursion, epiglottic inversion, UPDRS scores, and presence of coughing/throat clearing during meals. The search identified 13 studies specifically addressing the effects of DBS on swallowing. Critical assessment of the 13 identified peer-reviewed publications revealed nine studies employing an experimental design, (e.g. “on” vs. “off”, pre- vs. post-DBS) and four case reports. None of the nine experimental studies were found to identify clinically significant improvement or decline in swallowing function with DBS. Despite these findings, several common threads were identified across experimental studies and will be examined in this review. Additionally, available data demonstrate that, although subthalamic nucleus (STN) stimulation has been considered to cause more impairment to swallowing function than globus pallidus internus (GPi) stimulation, there are no experimental studies directly comparing swallowing function in STN vs. GPi. Moreover, there has been no comparison of unilateral vs. bilateral DBS surgery and the coincident effects on swallowing function. This review includes a critical analysis of all experimental studies and discusses methodological issues that should be addressed in future studies. PMID:23726461

  16. Body weight gain rate in patients with Parkinson's disease and deep brain stimulation.

    PubMed

    Barichella, Michela; Marczewska, Agnieszka M; Mariani, Claudio; Landi, Andrea; Vairo, Antonella; Pezzoli, Gianni

    2003-11-01

    We evaluated body weight changes in patients with Parkinson's disease (PD) after electrode implantation for deep brain stimulation (DBS) in the subthalamic nucleus (STN) in relation to clinical improvement. Thirty PD patients who received STN DBS were included (22 men, 8 women; mean age, 60.0 +/- 7.1 years; mean PD duration, 13.5 +/- 3.7 years; mean body mass index [BMI], 21.6 +/- 3.0 kg/m2). Body weight, physical activity, and Unified Parkinson's Disease Rating Scale (UPDRS) scores were noted before and 3 and 12 months after the procedure. Significant weight gain occurred in 29 patients; the mean increase was 14.8 +/- 9.8% of initial body weight in 1 year. Of the patients, 46.5% reported weight gain in the first 3 months, 21.4% gradual weight gain in the first 6 months, and 32.1% a slow increase for 1 year. Mean BMI increased up to 24.7 +/- 3.7 kg/m2. After 1 year, mean UPDRS motor score improved significantly in off and in on; and therapy complications improved by 91.0 +/- 17.0%. BMI changes at 3 and 12 months were significantly correlated to dyskinesia score changes, and levodopa dosage was not. In PD, STN DBS produces not only symptom control, but also weight gain. DBS candidates should be given nutritional counseling before the intervention to prevent rapid and/or excessive weight gain.

  17. Deep Brain Stimulation for Movement Disorders of Basal Ganglia Origin: Restoring Function or Functionality?

    PubMed

    Wichmann, Thomas; DeLong, Mahlon R

    2016-04-01

    Deep brain stimulation (DBS) is highly effective for both hypo- and hyperkinetic movement disorders of basal ganglia origin. The clinical use of DBS is, in part, empiric, based on the experience with prior surgical ablative therapies for these disorders, and, in part, driven by scientific discoveries made decades ago. In this review, we consider anatomical and functional concepts of the basal ganglia relevant to our understanding of DBS mechanisms, as well as our current understanding of the pathophysiology of two of the most commonly DBS-treated conditions, Parkinson's disease and dystonia. Finally, we discuss the proposed mechanism(s) of action of DBS in restoring function in patients with movement disorders. The signs and symptoms of the various disorders appear to result from signature disordered activity in the basal ganglia output, which disrupts the activity in thalamocortical and brainstem networks. The available evidence suggests that the effects of DBS are strongly dependent on targeting sensorimotor portions of specific nodes of the basal ganglia-thalamocortical motor circuit, that is, the subthalamic nucleus and the internal segment of the globus pallidus. There is little evidence to suggest that DBS in patients with movement disorders restores normal basal ganglia functions (e.g., their role in movement or reinforcement learning). Instead, it appears that high-frequency DBS replaces the abnormal basal ganglia output with a more tolerable pattern, which helps to restore the functionality of downstream networks.

  18. Reduction of influence of task difficulty on perceptual decision making by STN deep brain stimulation.

    PubMed

    Green, Nikos; Bogacz, Rafal; Huebl, Julius; Beyer, Ann-Kristin; Kühn, Andrea A; Heekeren, Hauke R

    2013-09-09

    Neurocomputational models of optimal decision making ascribe a crucial role-the computation of conflict between choice alternatives-to the subthalamic nucleus (STN). Specifically, these models predict that deep brain stimulation (DBS) of the STN will diminish the influence of decision conflict on decision making. In this work, patients with Parkinson's disease judged the direction of motion in random dot stimuli while ON and OFF DBS. To induce decision conflict, we varied the task difficulty (motion coherence), leading to increased reaction time (RT) in trials with greater task difficulty in healthy subjects. Results indicate that DBS significantly influences performance for perceptual decisions under high decision conflict. RT increased substantially OFF DBS as the task became more difficult, and a diffusion model best accounted for behavioral data. In contrast, ON DBS, the influence of task difficulty on RT was significantly reduced and a race model best accounted for the observed data. Individual data fits of evidence accumulation models demonstrate different information processing under distinct DBS states. Furthermore, ON DBS, speed-accuracy tradeoffs affected the magnitude of decision criterion adjustment significantly less compared to OFF DBS. Together, these findings suggest a crucial role for the STN in adjusting decision making during high-conflict trials in perceptual decision making.

  19. Closed-loop deep brain stimulation by pulsatile delayed feedback with increased gap between pulse phases.

    PubMed

    Popovych, Oleksandr V; Lysyansky, Borys; Tass, Peter A

    2017-04-21

    Computationally it was shown that desynchronizing delayed feedback stimulation methods are effective closed-loop techniques for the control of synchronization in ensembles of interacting oscillators. We here computationally design stimulation signals for electrical stimulation of neuronal tissue that preserve the desynchronizing delayed feedback characteristics and comply with mandatory charge deposit-related safety requirements. For this, the amplitude of the high-frequency (HF) train of biphasic charge-balanced pulses used by the standard HF deep brain stimulation (DBS) is modulated by the smooth feedback signals. In this way we combine the desynchronizing delayed feedback approach with the HF DBS technique. We show that such a pulsatile delayed feedback stimulation can effectively and robustly desynchronize a network of model neurons comprising subthalamic nucleus and globus pallidus external and suggest this approach for desynchronizing closed-loop DBS. Intriguingly, an interphase gap introduced between the recharging phases of the charge-balanced biphasic pulses can significantly improve the stimulation-induced desynchronization and reduce the amount of the administered stimulation. In view of the recent experimental and clinical studies indicating a superiority of the closed-loop DBS to open-loop HF DBS, our results may contribute to a further development of effective stimulation methods for the treatment of neurological disorders characterized by abnormal neuronal synchronization.

  20. Network effects and pathways in Deep brain stimulation in Parkinson's disease.

    PubMed

    Koirala, N; Fleischer, V; Granert, O; Deuschl, G; Muthuraman, M; Groppa, S

    2016-08-01

    Deep brain stimulation of subthalamic nucleus (STN-DBS) became a standard therapeutic option in Parkinson's disease (PD), even though the underlying modulated network of STN-DBS is still poorly described. Probabilistic tractography and connectivity analysis as derived from diffusion tensor imaging (DTI) were performed together with modelling of implanted electrode positions and linked postoperative clinical outcome. Fifteen patients with idiopathic PD without dementia were selected for DBS treatment. After pre-processing, probabilistic tractography was run from cortical and subcortical seeds of the hypothesized network to targets represented by the positions of the active DBS contacts. The performed analysis showed that the projections of the stimulation site to supplementary motor area (SMA) and primary motor cortex (M1) are mainly involved in the network effects of STN-DBS. An involvement of the "hyperdirected pathway" and a clear delimitation of the cortico-spinal tract were demonstrated. This study shows the effects of STN-DBS in PD distinctly rely on the network connections of the stimulated region to M1 and SMA, motor and premotor regions.

  1. Exploring risk factors for stuttering development in Parkinson disease after deep brain stimulation.

    PubMed

    Picillo, Marina; Vincos, Gustavo B; Sammartino, Francesco; Lozano, Andres M; Fasano, Alfonso

    2017-05-01

    Stuttering is a speech disorder with disruption of verbal fluency, occasionally present in Parkinson's disease (PD). PD co-incident stuttering may either worsen or improve after Deep Brain Stimulation (DBS). Sixteen out of 453 PD patients (3.5%) exhibited stuttering after DBS (PD-S) and were compared with a group of patients without stuttering (PD-NS) using non-parametric statistics. After DBS, stuttering worsened in 3 out of 4 patients with co-incidental stuttering. Most PD-S underwent subthalamic (STN) DBS, but 4 were implanted in the globus pallidus (GPi). Nine out of 16 PD-S (56.3%) reported a positive familial history for stuttering compared to none of the PD-NS. PD-S were mainly male (81.3%) with slight worse motor features compared to PD-NS. Herein, we describe a group of PD patients developing stuttering after DBS and report the presence of a positive familial history for stuttering as the most relevant risk factor, suggesting a possible underlying genetic cause. The fact that stuttering occurred after either STN or GPi DBS is an argument against the impact of medication reduction on stuttering. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Deep brain stimulation and medication for parkinsonian tremor during secondary tasks.

    PubMed

    Sturman, Molly M; Vaillancourt, David E; Metman, Leo Verhagen; Sierens, Diane K; Bakay, Roy A E; Corcos, Daniel M

    2007-06-15

    This study examined the efficacy of subthalamic nucleus (STN), deep brain stimulation (DBS), and medication for resting tremor during performance of secondary tasks. Hand tremor was recorded using accelerometry and electromyography (EMG) from 10 patients with Parkinson's disease (PD) and ten matched control subjects. The PD subjects were examined off treatment, on STN DBS, on medication, and on STN DBS plus medication. In the first experiment, tremor was recorded in a quiet condition and during a cognitive task designed to enhance tremor. In the second experiment, tremor was recorded in a quiet condition and during isometric finger flexion (motor task) with the contralateral limb at 5% of the maximal voluntary contraction (MVC) that was designed to suppress tremor. Results showed that: (1) STN DBS and medication reduced tremor during a cognitive task that exacerbated tremor, (2) STN DBS normalized tremor frequency in both the quiet and cognitive task conditions, whereas tremor amplitude was only normalized in the quiet condition, (3) a secondary motor task reduced tremor in a similar manner to STN DBS. These findings demonstrate that STN DBS still suppresses tremor in the presence of a cognitive task. Furthermore, a secondary motor task of the opposite limb suppresses tremor to levels comparable to STN DBS.

  3. Ultra-High Field Template-Assisted Target Selection for Deep Brain Stimulation Surgery.

    PubMed

    Lau, Jonathan C; MacDougall, Keith W; Arango, Miguel F; Peters, Terry M; Parrent, Andrew G; Khan, Ali R

    2017-07-01

    Template and atlas guidance are fundamental aspects of stereotactic neurosurgery. The recent availability of ultra-high field (7 Tesla) magnetic resonance imaging has enabled in vivo visualization at the submillimeter scale. In this Doing More with Less article, we describe our experiences with integrating ultra-high field template data into the clinical workflow to assist with target selection in deep brain stimulation (DBS) surgical planning. The creation of a high-resolution 7T template is described, generated from group data acquired at our center. A computational workflow was developed for spatially aligning the 7T template with standard clinical data and furthermore, integrating the derived imaging volumes into the surgical planning workstation. We demonstrate that our methodology can be effective for assisting with target selection in 2 cases: unilateral internal pallidum DBS for painful dystonia and bilateral subthalamic nucleus DBS for Parkinson's disease. In this article, we have described a workflow for the integration of high-resolution in vivo ultra-high field templates into the surgical navigation system as a means to assist with DBS planning. The method does not require any additional cost or time to the patient. Future work will include prospectively evaluating different templates and their impact on target selection. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  4. Effects of deep brain stimulation on vocal fold immobility in Parkinson's disease

    PubMed Central

    Arocho-Quinones, Elsa V.; Hammer, Michael J.; Bock, Jonathan M.; Pahapill, Peter A.

    2017-01-01

    Background: Vocal fold (VF) immobility is a rare, potentially fatal complication of advanced Parkinson's disease (PD). Previous reports suggest that subthalamic nucleus deep brain stimulation (STN-DBS) may influence laryngeal function, yet the role of STN-DBS on VF immobility remains unexplored. Case Description: We report a case of a patient with advanced PD and bilateral VF immobility ultimately requiring a tracheostomy. To assess the effects of STN-DBS on vocal cord function and to correlate these effects with peripheral motor symptoms at different stimulation settings, the patient was evaluated before and after initiation of bilateral STN-DBS. Measures included direct observation of VF mobility via transnasal laryngoscopy, levodopa equivalent dose of anti-PD medication, and motor scores. High frequency (150 Hz) STN-DBS resulted in improved motor scores, reduced medication requirement, and modestly improved right VF abduction although insufficient for safe decannulation. Low frequency (60 Hz) stimulation resulted in lower motor scores, but without worsening VF abduction. Conclusions: STN-DBS may play an important role in the neuromodulation of PD-induced laryngeal dysfunction, including VF mobility. Characterization of these axial symptoms is important when programming and evaluating responsiveness to DBS. PMID:28303202

  5. Deep Brain Stimulation Significantly Decreases Disability from Low Back Pain in Patients with Advanced Parkinson's Disease

    PubMed Central

    Smith, Heather; Gee, Lucy; Kumar, Vignessh; Ramirez-Zamora, Adolfo; Durphy, Jennifer; Hanspal, Era; Barba, Anne; Molho, Eric; Shin, Damian; Pilitsis, Julie G.

    2015-01-01

    Background Up to 60% of Parkinson's patients suffer from low back pain (LBP) during the course of their disease. How LBP affects daily functional status and how to manage this aspect of PD has not been adequately explored. Methods We examined sixteen patients undergoing bilateral subthalamic nucleus deep brain stimulation (STN DBS) who met inclusion criteria for moderate disability from LBP, as classified by the Oswestry Low Back Pain Disability Index (OLBPD). Results Thirteen of 16 patients had attempted additional treatments for LBP including medical management, massage, chiropractic, epidural steroid injections and/or surgery and with minimal relief. Following DBS, there was a significant improvement in OLBPD at both the 6-month and 1-year time points (p < 0.02, p < 0.005 respectively). A mean improvement of 31.7% on OLBPD score was noted. Visual Analogue Scale (VAS) similarly decreased significantly at 1 year (p = 0.015). There was no correlation between OLBPD score and other measures including UPDRS, age, and other non-motor symptoms. Conclusion Given the prevalent yet undertreated disability associated with LBP in PD, these results are novel in that they show STN DBS has a significant positive effect on disability associated with LBP. PMID:25895600

  6. System Identification of Local Field Potentials under Deep Brain Stimulation in a Healthy Primate

    PubMed Central

    Pedoto, Gilda; Santaniello, Sabato; Montgomery, Erwin B.; Gale, John T.; Fiengo, Giovanni; Glielmo, Luigi; Sarma, Sridevi V.

    2013-01-01

    High frequency (HF) Deep Brain Stimulation (DBS) in the Sub-Thalamic Nucleus (STN) is a clinically recognized therapy for the treatment of motor disorders in Parkinson Disease (PD). The underlying mechanisms of DBS and how it impacts neighboring nuclei, however, are not yet completely understood. Electrophysiological data has been collected in PD patients and primates to better understand the impact of DBS on STN and the entire Basal Ganglia (BG) motor circuit. We use single unit recordings from Globus Pallidus, both pars interna and externa segments (GPi and GPe) in the BG, in a normal primate before and after DBS to reconstruct Local Field Potentials (LFPs) in the region. We then use system identification techniques to understand how GPe LFP activity and the DBS signal applied to STN influence GPi LFP activity. Our models suggest that when no stimulation is applied, the GPe LFPs have an inhibitory effect on GPi LFPs with a 2-3 ms delay, as is the case for single unit neuronal activity. On the other hand, when DBS is ON the models suggest that stimulation has a dominant effect on GPi LFPs which mask the inhibitory effects of GPe. PMID:21096635

  7. Deep brain stimulation amplitude alters posture shift velocity in Parkinson's disease.

    PubMed

    Krishnamurthi, Narayanan; Mulligan, Stefani; Mahant, Padma; Samanta, Johan; Abbas, James J

    2012-08-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is now widely used to alleviate symptoms of Parkinson's disease (PD). The specific aim of this study was to identify posture control measures that may be used to improve selection of DBS parameters in the clinic and this was carried out by changing the DBS stimulation amplitude. A dynamic posture shift paradigm was used to assess posture control in 4 PD STN-DBS subjects. Each subject was tested at 4 stimulation amplitude settings. Movements of the center of pressure and the position of the pelvis were monitored and several quantitative indices were calculated. The presence of any statistically significant changes in several normalized indices due to reduced/no stimulation was tested using the one-sample t test. The peak velocity and the average movement velocity during the initial and mid phases of movement towards the target posture were substantially reduced. These results may be explained in terms of increased akinesia and bradykinesia due to altered stimulation conditions. Thus, the dynamic posture shift paradigm may be an effective tool to quantitatively characterize the effects of DBS on posture control and should be further investigated as a tool for selection of DBS parameters in the clinic.

  8. Post-operative assessment in Deep Brain Stimulation based on multimodal images: registration workflow and validation

    NASA Astrophysics Data System (ADS)

    Lalys, Florent; Haegelen, Claire; Abadie, Alexandre; Jannin, Pierre

    2009-02-01

    Object Movement disorders in Parkinson disease patients may require functional surgery, when medical therapy isn't effective. In Deep Brain Stimulation (DBS) electrodes are implanted within the brain to stimulate deep structures such as SubThalamic Nucleus (STN). This paper describes successive steps for constructing a digital Atlas gathering patient's location of electrodes and contacts for post operative assessment. Materials and Method 12 patients who had undergone bilateral STN DBS have participated to the study. Contacts on post-operative CT scans were automatically localized, based on black artefacts. For each patient, post operative CT images were rigidly registered to pre operative MR images. Then, pre operative MR images were registered to a MR template (super-resolution Collin27 average MRI template). This last registration was the combination of global affine, local affine and local non linear registrations, respectively. Four different studies were performed in order to validate the MR patient to template registration process, based on anatomical landmarks and clinical scores (i.e., Unified Parkinson's disease rating Scale). Visualisation software was developed for displaying into the template images the stimulated contacts represented as cylinders with a colour code related to the improvement of the UPDRS. Results The automatic contact localization algorithm was successful for all the patients. Validation studies for the registration process gave a placement error of 1.4 +/- 0.2 mm and coherence with UPDRS scores. Conclusion The developed visualization tool allows post-operative assessment for previous interventions. Correlation with additional clinical scores will certainly permit to learn more about DBS and to better understand clinical side-effects.

  9. Decoding gripping force based on local field potentials recorded from subthalamic nucleus in humans.

    PubMed

    Tan, Huiling; Pogosyan, Alek; Ashkan, Keyoumars; Green, Alexander L; Aziz, Tipu; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Hariz, Marwan; Brown, Peter

    2016-11-18

    The basal ganglia are known to be involved in the planning, execution and control of gripping force and movement vigour. Here we aim to define the nature of the basal ganglia control signal for force and to decode gripping force based on local field potential (LFP) activities recorded from the subthalamic nucleus (STN) in patients with deep brain stimulation (DBS) electrodes. We found that STN LFP activities in the gamma (55-90 Hz) and beta (13-30m Hz) bands were most informative about gripping force, and that a first order dynamic linear model with these STN LFP features as inputs can be used to decode the temporal profile of gripping force. Our results enhance the understanding of how the basal ganglia control gripping force, and also suggest that deep brain LFPs could potentially be used to decode movement parameters related to force and movement vigour for the development of advanced human-machine interfaces.

  10. Theoretical Analysis of the Local Field Potential in Deep Brain Stimulation Applications

    PubMed Central

    Lempka, Scott F.; McIntyre, Cameron C.

    2013-01-01

    Deep brain stimulation (DBS) is a common therapy for treating movement disorders, such as Parkinson’s disease (PD), and provides a unique opportunity to study the neural activity of various subcortical structures in human patients. Local field potential (LFP) recordings are often performed with either intraoperative microelectrodes or DBS leads and reflect oscillatory activity within nuclei of the basal ganglia. These LFP recordings have numerous clinical implications and might someday be used to optimize DBS outcomes in closed-loop systems. However, the origin of the recorded LFP is poorly understood. Therefore, the goal of this study was to theoretically analyze LFP recordings within the context of clinical DBS applications. This goal was achieved with a detailed recording model of beta oscillations (∼20 Hz) in the subthalamic nucleus. The recording model consisted of finite element models of intraoperative microelectrodes and DBS macroelectrodes implanted in the brain along with multi-compartment cable models of STN projection neurons. Model analysis permitted systematic investigation into a number of variables that can affect the composition of the recorded LFP (e.g. electrode size, electrode impedance, recording configuration, and filtering effects of the brain, electrode-electrolyte interface, and recording electronics). The results of the study suggest that the spatial reach of the LFP can extend several millimeters. Model analysis also showed that variables such as electrode geometry and recording configuration can have a significant effect on LFP amplitude and spatial reach, while the effects of other variables, such as electrode impedance, are often negligible. The results of this study provide insight into the origin of the LFP and identify variables that need to be considered when analyzing LFP recordings in clinical DBS applications. PMID:23555799

  11. Theoretical analysis of the local field potential in deep brain stimulation applications.

    PubMed

    Lempka, Scott F; McIntyre, Cameron C

    2013-01-01

    Deep brain stimulation (DBS) is a common therapy for treating movement disorders, such as Parkinson's disease (PD), and provides a unique opportunity to study the neural activity of various subcortical structures in human patients. Local field potential (LFP) recordings are often performed with either intraoperative microelectrodes or DBS leads and reflect oscillatory activity within nuclei of the basal ganglia. These LFP recordings have numerous clinical implications and might someday be used to optimize DBS outcomes in closed-loop systems. However, the origin of the recorded LFP is poorly understood. Therefore, the goal of this study was to theoretically analyze LFP recordings within the context of clinical DBS applications. This goal was achieved with a detailed recording model of beta oscillations (∼20 Hz) in the subthalamic nucleus. The recording model consisted of finite element models of intraoperative microelectrodes and DBS macroelectrodes implanted in the brain along with multi-compartment cable models of STN projection neurons. Model analysis permitted systematic investigation into a number of variables that can affect the composition of the recorded LFP (e.g. electrode size, electrode impedance, recording configuration, and filtering effects of the brain, electrode-electrolyte interface, and recording electronics). The results of the study suggest that the spatial reach of the LFP can extend several millimeters. Model analysis also showed that variables such as electrode geometry and recording configuration can have a significant effect on LFP amplitude and spatial reach, while the effects of other variables, such as electrode impedance, are often negligible. The results of this study provide insight into the origin of the LFP and identify variables that need to be considered when analyzing LFP recordings in clinical DBS applications.

  12. Deep brain stimulation surgery for alcohol addiction.

    PubMed

    Voges, Juergen; Müller, Ulf; Bogerts, Bernhard; Münte, Thomas; Heinze, Hans-Jochen

    2013-01-01

    The consequences of chronic alcohol dependence cause important health and economic burdens worldwide. Relapse rates after standard treatment (medication and psychotherapy) are high. There is evidence from in vivo investigations and from studies in patients that the brain's reward system is critically involved in the development and maintenance of addictive behavior, suggesting that modification of this system could significantly improve the prognosis of addictive patients. Motivated by an accidental observation, we used the nucleus accumbens (NAc), which has a central position in the dopaminergic reward system for deep brain stimulation (DBS) of alcohol addiction. We report our first experiences with NAc DBS for alcohol dependence and review the literature addressing the mechanisms leading to addiction. Five patients were treated off-label with bilateral NAc DBS for severe alcohol addiction (average follow-up 38 months). All patients experienced significant and ongoing improvement of craving. Two patients remained completely abstinent for more than 4 years. NAc stimulation was tolerated without permanent side effects. Simultaneous recording of local field potentials from the target area and surface electroencephalography while patients performed neuropsychological tasks gave a hint on the pivotal role of the NAc in processing alcohol-related cues. To our knowledge, the data presented here reflect the first attempt to treat alcohol-addicted patients with NAc DBS. Electrical NAc stimulation probably counterbalances the effect of drug-related stimuli triggering involuntarily drug-seeking behavior. Meanwhile, two prospective clinical studies using randomized, double-blind, and crossover stimulation protocols for DBS are underway to corroborate these preliminary results. Published by Elsevier Inc.

  13. Closing the loop of deep brain stimulation

    PubMed Central

    Carron, Romain; Chaillet, Antoine; Filipchuk, Anton; Pasillas-Lépine, William; Hammond, Constance

    2013-01-01

    High-frequency deep brain stimulation is used to treat a wide range of brain disorders, like Parkinson's disease. The stimulated networks usually share common electrophysiological signatures, including hyperactivity and/or dysrhythmia. From a clinical perspective, HFS is expected to alleviate clinical signs without generating adverse effects. Here, we consider whether the classical open-loop HFS fulfills these criteria and outline current experimental or theoretical research on the different types of closed-loop DBS that could provide better clinical outcomes. In the first part of the review, the two routes followed by HFS-evoked axonal spikes are explored. In one direction, orthodromic spikes functionally de-afferent the stimulated nucleus from its downstream target networks. In the opposite direction, antidromic spikes prevent this nucleus from being influenced by its afferent networks. As a result, the pathological synchronized activity no longer propagates from the cortical networks to the stimulated nucleus. The overall result can be described as a reversible functional de-afferentation of the stimulated nucleus from its upstream and downstream nuclei. In the second part of the review, the latest advances in closed-loop DBS are considered. Some of the proposed approaches are based on mathematical models, which emphasize different aspects of the parkinsonian basal ganglia: excessive synchronization, abnormal firing-rate rhythms, and a deficient thalamo-cortical relay. The stimulation strategies are classified depending on the control-theory techniques on which they are based: adaptive and on-demand stimulation schemes, delayed and multi-site approaches, stimulations based on proportional and/or derivative control actions, optimal control strategies. Some of these strategies have been validated experimentally, but there is still a large reservoir of theoretical work that may point to ways of improving practical treatment. PMID:24391555

  14. Brain tumor segmentation with Deep Neural Networks.

    PubMed

    Havaei, Mohammad; Davy, Axel; Warde-Farley, David; Biard, Antoine; Courville, Aaron; Bengio, Yoshua; Pal, Chris; Jodoin, Pierre-Marc; Larochelle, Hugo

    2017-01-01

    In this paper, we present a fully automatic brain tumor segmentation method based on Deep Neural Networks (DNNs). The proposed networks are tailored to glioblastomas (both low and high grade) pictured in MR images. By their very nature, these tumors can appear anywhere in the brain and have almost any kind of shape, size, and contrast. These reasons motivate our exploration of a machine learning solution that exploits a flexible, high capacity DNN while being extremely efficient. Here, we give a description of different model choices that we've found to be necessary for obtaining competitive performance. We explore in particular different architectures based on Convolutional Neural Networks (CNN), i.e. DNNs specifically adapted to image data. We present a novel CNN architecture which differs from those traditionally used in computer vision. Our CNN exploits both local features as well as more global contextual features simultaneously. Also, different from most traditional uses of CNNs, our networks use a final layer that is a convolutional implementation of a fully connected layer which allows a 40 fold speed up. We also describe a 2-phase training procedure that allows us to tackle difficulties related to the imbalance of tumor labels. Finally, we explore a cascade architecture in which the output of a basic CNN is treated as an additional source of information for a subsequent CNN. Results reported on the 2013 BRATS test data-set reveal that our architecture improves over the currently published state-of-the-art while being over 30 times faster. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Analysis of simultaneous MEG and intracranial LFP recordings during Deep Brain Stimulation: a protocol and experimental validation

    PubMed Central

    Oswal, Ashwini; Jha, Ashwani; Neal, Spencer; Reid, Alphonso; Bradbury, David; Aston, Peter; Limousin, Patricia; Foltynie, Tom; Zrinzo, Ludvic; Brown, Peter; Litvak, Vladimir

    2016-01-01

    Background Deep Brain Stimulation (DBS) is an effective treatment for several neurological and psychiatric disorders. In order to gain insights into the therapeutic mechanisms of DBS and to advance future therapies a better understanding of the effects of DBS on large-scale brain networks is required. New method In this paper, we describe an experimental protocol and analysis pipeline for simultaneously performing DBS and intracranial local field potential (LFP) recordings at a target brain region during concurrent magnetoencephalography (MEG) measurement. Firstly we describe a phantom setup that allowed us to precisely characterise the MEG artefacts that occurred during DBS at clinical settings. Results Using the phantom recordings we demonstrate that with MEG beamforming it is possible to recover oscillatory activity synchronised to a reference channel, despite the presence of high amplitude artefacts evoked by DBS. Finally, we highlight the applicability of these methods by illustrating in a single patient with Parkinson's disease (PD), that changes in cortical-subthalamic nucleus coupling can be induced by DBS. Comparison with existing approaches To our knowledge this paper provides the first technical description of a recording and analysis pipeline for combining simultaneous cortical recordings using MEG, with intracranial LFP recordings of a target brain nucleus during DBS. PMID:26698227

  16. Tremor-correlated neuronal activity in the subthalamic nucleus of Parkinsonian patients.

    PubMed

    Amtage, Florian; Henschel, Kathrin; Schelter, Björn; Vesper, Jan; Timmer, Jens; Lücking, Carl Hermann; Hellwig, Bernhard

    2008-09-19

    Tremor in Parkinson's disease (PD) is generated by an oscillatory neuronal network consisting of cortex, basal ganglia and thalamus. The subthalamic nucleus (STN) which is part of the basal ganglia is of particular interest, since deep brain stimulation of the STN is an effective treatment for PD including Parkinsonian tremor. It is controversial if and how the STN contributes to tremor generation. In this study, we analyze neuronal STN activity in seven patients with Parkinsonian rest tremor who underwent stereotactic surgery for deep brain stimulation. Surface EMG was recorded from the wrist flexors and extensors. Simultaneously, neuronal spike activity was registered in different depths of the STN using an array of five microelectrodes. After spike-sorting, spectral coherence was analyzed between spike activity of STN neurons and tremor activity. Significant coherence at the tremor frequency was detected between EMG and neuronal STN activity in 76 out of 145 neurons (52.4%). In contrast, coherence in the beta band occurred only in 10 out of 145 neurons (6.9%). Tremor-coherent STN activity was widely distributed over the STN being more frequent in its dorsal parts (70.8-88.9%) than in its ventral parts (25.0-48.0%). Our results suggest that synchronous neuronal STN activity at the tremor frequency contributes to the pathogenesis of Parkinsonian tremor. The wide-spread spatial distribution of tremor-coherent spike activity argues for the recruitment of an extended network of subthalamic neurons for tremor generation.

  17. Deep brain stimulation for monogenic dystonia.

    PubMed

    Aravamuthan, Bhooma R; Waugh, Jeff L; Stone, Scellig S

    2017-09-12

    Deep brain stimulation (DBS) has recently emerged as an important management option in children with medically refractory dystonia. DBS is most commonly used, best studied, and thought to be most efficacious for a select group of childhood or adolescent onset monogenic dystonias (designated with a standard 'DYT' prefix). We review how to clinically recognize these types of dystonia and the relative efficacy of DBS for key monogenic dystonias. Though used for dystonia in adults for several years, DBS has only lately been used in children. Recent evidence shows that patients with shorter duration of dystonia often experience greater benefit following DBS. This suggests that early recognition of the appropriate dystonic phenotypes and consideration of DBS in these patients may improve the management of dystonia. DBS should be considered early in patients who have medically refractory dystonia, especially for the monogenic dystonias that have a high response rate to DBS. It is important to differentiate between these monogenic dystonias and dystonias of other causes to properly prognosticate for these patients and to determine whether DBS is an appropriate management option.

  18. Deep Brain Stimulation, Authenticity and Value.

    PubMed

    Nyholm, Sven; O'Neill, Elizabeth

    2017-10-01

    In this article, we engage in dialogue with Jonathan Pugh, Hannah Maslen, and Julian Savulescu about how to best interpret the potential impacts of deep brain stimulation on the self. We consider whether ordinary peoples' convictions about the true self should be interpreted in essentialist or existentialist ways. Like Pugh, Maslen, and Savulescu, we argue that it is useful to understand the notion of the true self as having both essentialist and existentialist components. We also consider two ideas from existentialist philosophy-Jean-Paul Sartre and Simone de Beauvoir's ideas about "bad faith" and "ambiguity"-to argue that there can be value to patients in regarding themselves as having a certain amount of freedom to choose what aspects of themselves should be considered representative of their true selves. Lastly, we consider the case of an anorexia nervosa patient who shifts between conflicting mind-sets. We argue that mind-sets in which it is easier for the patient and his or her family to share values can plausibly be considered to be more representative of the patient's true self, if this promotes a well-functioning relationship between the patient and the family. However, we also argue that families are well advised to give patients room to determine what such shared values mean to them, as it can be alienating for patients if they feel that others try to impose values on them from the outside.

  19. Deep brain stimulation: how does it work?

    PubMed

    Agnesi, Filippo; Johnson, Matthew D; Vitek, Jerrold L

    2013-01-01

    Chronic deep brain stimulation (DBS) has become a widely accepted surgical treatment for medication-refractory movement disorders and is under evaluation for a variety of neurological disorders. In order to create opportunities to improve treatment efficacy, streamline parameter selection, and foster new potential applications, it is important to have a clear and comprehensive understanding of how DBS works. Although early hypothesis proposed that high-frequency electrical stimulation inhibited neuronal activity proximal to the active electrode, recent studies have suggested that the output of the stimulated nuclei is paradoxically activated by DBS. Such regular, time-locked output is thought to override the transmission of pathological bursting and oscillatory activity through the stimulated nuclei, as well as inducing synaptic plasticity and network reorganization. This chapter reviews electrophysiological experiments, biochemical analyses, computer modeling and imaging studies positing that, although general principles exist, the therapeutic mechanism(s) of action depend both on the site of stimulation and on the disorder being treated. © 2013 Elsevier B.V. All rights reserved.

  20. A direct relationship between oscillatory subthalamic nucleus-cortex coupling and rest tremor in Parkinson's disease.

    PubMed

    Hirschmann, Jan; Hartmann, Christian J; Butz, Markus; Hoogenboom, Nienke; Ozkurt, Tolga E; Elben, Saskia; Vesper, Jan; Wojtecki, Lars; Schnitzler, Alfons

    2013-12-01

    Electrophysiological studies suggest that rest tremor in Parkinson's disease is associated with an alteration of oscillatory activity. Although it is well known that tremor depends on cortico-muscular coupling, it is unclear whether synchronization within and between brain areas is specifically related to the presence and severity of tremor. To tackle this longstanding issue, we took advantage of naturally occurring spontaneous tremor fluctuations and investigated cerebral synchronization in the presence and absence of rest tremor. We simultaneously recorded local field potentials from the subthalamic nucleus, the magnetoencephalogram and the electromyogram of forearm muscles in 11 patients with Parkinson's disease (all male, age: 52-74 years). Recordings took place the day after surgery for deep brain stimulation, after withdrawal of anti-parkinsonian medication. We selected epochs containing spontaneous rest tremor and tremor-free epochs, respectively, and compared power and coherence between subthalamic nucleus, cortex and muscle across conditions. Tremor-associated changes in cerebro-muscular coherence were localized by Dynamic Imaging of Coherent Sources. Subsequently, cortico-cortical coupling was analysed by computation of the imaginary part of coherency, a coupling measure insensitive to volume conduction. After tremor onset, local field potential power increased at individual tremor frequency and cortical power decreased in the beta band (13-30 Hz). Sensor level subthalamic nucleus-cortex, cortico-muscular and subthalamic nucleus-muscle coherence increased during tremor specifically at tremor frequency. The increase in subthalamic nucleus-cortex coherence correlated with the increase in electromyogram power. On the source level, we observed tremor-associated increases in cortico-muscular coherence in primary motor cortex, premotor cortex and posterior parietal cortex contralateral to the tremulous limb. Analysis of the imaginary part of coherency revealed

  1. Effects of deep brain stimulation on balance and gait in patients with Parkinson's disease: A systematic neurophysiological review.

    PubMed

    Collomb-Clerc, A; Welter, M-L

    2015-11-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) and internal globus pallidus (GPi) deep brain stimulation (DBS) provides an efficient treatment for the alleviation of motor signs in patients with Parkinson's disease. The effects of DBS on gait and balance disorders are less successful and may even lead to an aggravation of freezing of gait and imbalance. The identification of a substantia nigra pars reticulata (SNr)-mesencephalic locomotor region (MLR) network in the control of locomotion and postural control and of its dysfunction/lesion in PD patients with gait and balance disorders led to suggestion that DBS should be targeting the SNr and the pedunculopontine nucleus (part of the MLR) for PD patients with these disabling axial motor signs. However, the clinical results to date have been disappointing. In this review, we discuss the effects of DBS of these basal ganglia and brainstem structures on the neurophysiological parameters of gait and balance control in PD patients. Overall, the data suggest that both STN and GPi-DBS improve gait parameters and quiet standing postural control in PD patients, but have no effect or may even aggravate dynamic postural control, in particular with STN-DBS. Conversely, DBS of the SNr and PPN has no effect on gait parameters but improves anticipatory postural adjustments and gait postural control.

  2. Stochastic Phase Resetting: a Theory for Deep Brain Stimulation

    NASA Astrophysics Data System (ADS)

    Tass, Peter A.

    2000-03-01

    A stochastic approach to phase resetting in clusters of interacting oscillators is presented. This theory explains how a stimulus, especially a single pulse, induces synchronization and desynchronization processes. The theory is used to design a new technique for deep brain stimulation in patients suffering from Parkinson's disease or essential tremor that do no longer respond to drug therapy. This stimulation mode is a feedback controlled single pulse stimulation. The feedback signal is registered with the deep brain electrode, and the desynchronizing pulses are administered via the same electrode. The stochastic phase resetting theory is used as a starting point of a model based design of intelligent and gentle deep brain stimulation techniques.

  3. "Asleep" deep brain stimulation for essential tremor.

    PubMed

    Chen, Tsinsue; Mirzadeh, Zaman; Chapple, Kristina; Lambert, Margaret; Dhall, Rohit; Ponce, Francisco A

    2016-06-01

    OBJECT Deep brain stimulation (DBS) performed under general anesthesia ("asleep" DBS) has not been previously reported for essential tremor. This is in part due to the inability to visualize the target (the ventral intermediate nucleus [VIM]) on MRI. The authors evaluate the efficacy of this asleep technique in treating essential tremor by indirect VIM targeting. METHODS The authors retrospectively reviewed consecutive cases of initial DBS for essential tremor performed by a single surgeon. DBS was performed with patients awake (n = 40, intraoperative test stimulation without microelectrode recording) or asleep (n = 17, under general anesthesia). Targeting proceeded with standardized anatomical coordinates on preoperative MRI. Intraoperative CT was used for stereotactic registration and lead position confirmation. Functional outcomes were evaluated with pre- and postoperative Bain and Findley Tremor Activities of Daily Living scores. RESULTS A total of 29 leads were placed in asleep patients, and 60 were placed in awake patients. Bain and Findley Tremor Activities of Daily Living Questionnaire scores were not significantly different preoperatively for awake versus asleep cohorts (p = 0.2). The percentage of postoperative improvement was not significantly different between asleep (48.6%) and awake (45.5%) cohorts (p = 0.35). Euclidean error (mm) was higher for awake versus asleep patients (1.7 ± 0.8 vs 1.2 ± 0.4, p = 0.01), and radial error (mm) trended higherfor awake versus asleep patients (1.3 ± 0.8 vs 0.9 ± 0.5, p = 0.06). There were no perioperative complications. CONCLUSIONS In the authors' initial experience, asleep VIM DBS for essential tremor without intraoperative test stimulation can be performed safely and effectively.

  4. Deep brain and cortical stimulation for epilepsy.

    PubMed

    Sprengers, Mathieu; Vonck, Kristl; Carrette, Evelien; Marson, Anthony G; Boon, Paul

    2014-06-17

    Despite optimal medical treatment, including epilepsy surgery, many epilepsy patients have uncontrolled seizures. In the last decades, interest has grown in invasive intracranial neurostimulation as a treatment for these patients. Intracranial stimulation includes both deep brain stimulation (DBS) (stimulation through depth electrodes) and cortical stimulation (subdural electrodes). To assess the efficacy, safety and tolerability of deep brain and cortical stimulation for refractory epilepsy based on randomized controlled trials. We searched PubMed (6 August 2013), the Cochrane Epilepsy Group Specialized Register (31 August 2013), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 7 of 12) and reference lists of retrieved articles. We also contacted device manufacturers and other researchers in the field. No language restrictions were imposed. Randomized controlled trials (RCTs) comparing deep brain or cortical stimulation to sham stimulation, resective surgery or further treatment with antiepileptic drugs. Four review authors independently selected trials for inclusion. Two review authors independently extracted the relevant data and assessed trial quality and overall quality of evidence. The outcomes investigated were seizure freedom, responder rate, percentage seizure frequency reduction, adverse events, neuropsychological outcome and quality of life. If additional data were needed, the study investigators were contacted. Results were analysed and reported separately for different intracranial targets for reasons of clinical heterogeneity. Ten RCTs comparing one to three months of intracranial neurostimulation to sham stimulation were identified. One trial was on anterior thalamic DBS (n = 109; 109 treatment periods); two trials on centromedian thalamic DBS (n = 20; 40 treatment periods), but only one of the trials (n = 7; 14 treatment periods) reported sufficient information for inclusion in the quantitative meta

  5. Deep brain stimulation and cognitive decline in Parkinson's disease: The predictive value of electroencephalography.

    PubMed

    Markser, A; Maier, Franziska; Lewis, C J; Dembek, T A; Pedrosa, D; Eggers, C; Timmermann, L; Kalbe, E; Fink, G R; Burghaus, Lothar

    2015-10-01

    Some Parkinson's disease (PD) patients treated with subthalamic nucleus deep brain stimulation (STN-DBS) develop new-onset cognitive decline. We examined whether clinical EEG recordings can be used to predict cognitive deterioration in PD patients undergoing STN-DBS. In this retrospective study, we used the Grand Total EEG (GTE)-score (short and total) to evaluate pre- and postoperative EEGs. In PD patients undergoing STN-DBS (N = 30), cognitive functioning was measured using Mini-Mental State Test and DemTect before and after surgery. Severity of motor impairment was assessed using the Unified Parkinson's Disease Rating Scale-III. Patients were classified into patients with or without cognitive decline after STN-DBS surgery. Epidemiological data, pre- and postoperative EEG recordings as well as neuropsychological and neurological data, electrode positions and the third ventricle width were compared. A logistic regression model was used to identify predictors of cognitive decline. Motor deficits significantly improved from pre- to post-surgery, while the mean GTE-scores increased significantly. Six patients developed cognitive deterioration 4-12 months postoperatively. These patients had significantly higher preoperative GTE-scores than patients without cognitive deterioration, although preoperative cognitive functioning was comparable. Electrode positions, brain atrophy and neurological data did not differ between groups. Logistic regression analysis identified the GTE-score as a significant predictor of postoperative cognitive deterioration. Data suggest that the preoperative GTE-score can be used to identify PD patients that are at high risk for developing cognitive deterioration after STN-DBS surgery even though their preoperative cognitive state was normal.

  6. Testing different paradigms to optimize antidepressant deep brain stimulation in different rat models of depression.

    PubMed

    Rummel, Julia; Voget, Mareike; Hadar, Ravit; Ewing, Samuel; Sohr, Reinhard; Klein, Julia; Sartorius, Alexander; Heinz, Andreas; Mathé, Aleksander A; Vollmayr, Barbara; Winter, Christine

    2016-10-01

    Deep brain stimulation (DBS) of several targets induces beneficial responses in approximately 60% of patients suffering from treatment-resistant depression (TRD). The remaining 40% indicate that these stimulation sites do not bear therapeutic relevance for all TRD patients and consequently DBS-targets should be selected according to individual symptom profiles. We here used two animal models of depression known to have different genetic backgrounds and behavioral responses: the therapy-responsive Flinders sensitive line (FSL) and the therapy-refractory congenitally learned helpless rats (cLH) to study symptom-specific DBS effects i) of different brain sites ii) at different stimulation parameters, and iii) at different expressions of the disease. Sham-stimulation/DBS was applied chronic-intermittently or chronic-continuously to either the ventromedial prefrontal cortex (vmPFC, rodent equivalent to subgenual cingulate), nucleus accumbens (Nacc) or subthalamic nucleus (STN), and effects were studied on different depression-associated behaviors, i.e. anhedonia, immobility/behavioral despair and learned helplessness. Biochemical substrates of behaviorally effective versus ineffective DBS were analyzed using in-vivo microdialysis and post-mortem high-performance liquid chromatography (HPLC). We found that i) vmPFC-DBS outperforms Nacc-DBS, ii) STN-DBS increases depressive states, iii) chronic-continuous DBS does not add benefits compared to chronic-intermittent DBS, iv) DBS-efficacy depends on the disease expression modeled and iv) antidepressant DBS is associated with an increase in serotonin turnover alongside site-specific reductions in serotonin contents. The reported limited effectiveness of vmPFC DBS suggests that future research may consider the specific disease expression, investigation of different DBS-targets and alternative parameter settings. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Moving forward: advances in the treatment of movement disorders with deep brain stimulation.

    PubMed

    Schiefer, Terry K; Matsumoto, Joseph Y; Lee, Kendall H

    2011-01-01

    The modern era of stereotactic and functional neurosurgery has ushered in state of the art technologies for the treatment of movement disorders, particularly Parkinson's disease (PD), tremor, and dystonia. After years of experience with various surgical therapies, the eventual shortcomings of both medical and surgical treatments, and several serendipitous discoveries, deep brain stimulation (DBS) has risen to the forefront as a highly effective, safe, and reversible treatment for these conditions. Idiopathic advanced PD can be treated with thalamic, globus pallidus internus (GPi), or subthalamic nucleus (STN) DBS. Thalamic DBS primarily relieves tremor while GPi and STN DBS alleviate a wide range of Parkinsonian symptoms. Thalamic DBS is also used in the treatment of other types of tremor, particularly essential tremor, with excellent results. Both primary and various types of secondary dystonia can be treated very effectively with GPi DBS. The variety of anatomical targets for these movement disorders is indicative of the network-level dysfunction mediating these movement disturbances. Despite an increasing understanding of the clinical benefits of DBS, little is known about how DBS can create such wide sweeping neuromodulatory effects. The key to improving this therapeutic modality and discovering new ways to treat these and other neurologic conditions lies in better understanding the intricacies of DBS. Here we review the history and pertinent clinical data for DBS treatment of PD, tremor, and dystonia. While multiple regions of the brain have been targeted for DBS in the treatment of these movement disorders, this review article focuses on those that are most commonly used in current clinical practice. Our search criteria for PubMed included combinations of the following terms: DBS, neuromodulation, movement disorders, PD, tremor, dystonia, and history. Dates were not restricted.

  8. Moving Forward: Advances in the Treatment of Movement Disorders with Deep Brain Stimulation

    PubMed Central

    Schiefer, Terry K.; Matsumoto, Joseph Y.; Lee, Kendall H.

    2011-01-01

    The modern era of stereotactic and functional neurosurgery has ushered in state of the art technologies for the treatment of movement disorders, particularly Parkinson’s disease (PD), tremor, and dystonia. After years of experience with various surgical therapies, the eventual shortcomings of both medical and surgical treatments, and several serendipitous discoveries, deep brain stimulation (DBS) has risen to the forefront as a highly effective, safe, and reversible treatment for these conditions. Idiopathic advanced PD can be treated with thalamic, globus pallidus internus (GPi), or subthalamic nucleus (STN) DBS. Thalamic DBS primarily relieves tremor while GPi and STN DBS alleviate a wide range of Parkinsonian symptoms. Thalamic DBS is also used in the treatment of other types of tremor, particularly essential tremor, with excellent results. Both primary and various types of secondary dystonia can be treated very effectively with GPi DBS. The variety of anatomical targets for these movement disorders is indicative of the network-level dysfunction mediating these movement disturbances. Despite an increasing understanding of the clinical benefits of DBS, little is known about how DBS can create such wide sweeping neuromodulatory effects. The key to improving this therapeutic modality and discovering new ways to treat these and other neurologic conditions lies in better understanding the intricacies of DBS. Here we review the history and pertinent clinical data for DBS treatment of PD, tremor, and dystonia. While multiple regions of the brain have been targeted for DBS in the treatment of these movement disorders, this review article focuses on those that are most commonly used in current clinical practice. Our search criteria for PubMed included combinations of the following terms: DBS, neuromodulation, movement disorders, PD, tremor, dystonia, and history. Dates were not restricted. PMID:22084629

  9. Do Stable Patients With a Premorbid Depression History Have a Worse Outcome After Deep Brain Stimulation for Parkinson Disease?

    PubMed Central

    Okun, Michael S.; Wu, Samuel S.; Foote, Kelly D.; Bowers, Dawn; Gogna, Shilpa; Price, Catherine; Malaty, Irene; Rodriguez, Ramon L.; Jacobson, Charles E.; Ward, Herbert

    2013-01-01

    BACKGROUND Deep brain stimulation (DBS) has been associated with mood sequelae in a subset of patients operated on in either the subthalamic nucleus or the globus pallidus internus for the treatment of Parkinson disease. OBJECTIVE To compare mood and motor outcomes in those with and without a presurgical history of depression. METHODS Unilateral subthalamic nucleus or unilateral globus pallidus internus DBS patients followed up for a minimum of 6 months were included. All patients underwent a comprehensive outpatient psychiatric evaluation by a board-certified psychiatrist. Psychiatric diagnoses were based on Diagnostic and Statistical Manual, fourth edition, text revision, nomenclature (American Psychiatric Association, 2000). Motor and mood outcomes were compared. RESULTS A total of 110 patients were included. There were no significant differences in baseline variables between the 2 groups. Those with a preoperative history of depression had significantly higher Beck Depression Inventory scores than the nondepression group after DBS (8.97 ± 7.55 vs 5.92 ± 5.71; P = .04). Patients with a depression history had less improvement (11.6%) in pre/post-DBS change when Unified Parkinson Disease Rating Scale motor scores were compared (P = .03) after adjustment for stimulation site and baseline demographic and clinical variables. Patients with a higher levodopa equivalent dose had a worse clinical motor outcome. CONCLUSION Patients with a preoperative depression history had higher Beck Depression Inventory scores after DBS and significantly less (albeit small) improvement in pre/post-DBS change in Unified Parkinson Disease Rating Scale motor scores than patients without a history of depression. PMID:21415789

  10. Toward defining deep brain stimulation targets in MNI space: A subcortical atlas based on multimodal MRI, histology and structural connectivity.

    PubMed

    Ewert, Siobhan; Plettig, Philip; Li, Ningfei; Chakravarty, M Mallar; Collins, D Louis; Herrington, Todd M; Kühn, Andrea A; Horn, Andreas

    2017-05-20

    Three-dimensional atlases of subcortical brain structures are valuable tools to reference anatomy in neuroscience and neurology. For instance, they can be used to study the position and shape of the three most common deep brain stimulation (DBS) targets, the subthalamic nucleus (STN), internal part of the pallidum (GPi) and ventral intermediate nucleus of the thalamus (VIM) in spatial relationship to DBS electrodes. Here, we present a composite atlas based on manual segmentations of a multimodal high resolution brain template, histology and structural connectivity. In a first step, four key structures were defined on the template itself using a combination of multispectral image analysis and manual segmentation. Second, these structures were used as anchor points to coregister a detailed histological atlas into standard space. Results show that this approach significantly improved coregistration accuracy over previously published methods. Finally, a sub-segmentation of STN and GPi into functional zones was achieved based on structural connectivity. The result is a composite atlas that defines key nuclei on the template itself, fills the gaps between them using histology and further subdivides them using structural connectivity. We show that the atlas can be used to segment DBS targets in single subjects, yielding more accurate results compared to priorly published atlases. The atlas will be made publicly available and constitutes a resource to study DBS electrode localizations in combination with modern neuroimaging methods. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Analysis of Gene Expression Changes in the Rat Hippocampus After Deep Brain Stimulation of the Anterior Thalamic Nucleus

    PubMed Central

    Selvakumar, Tharakeswari; Alavian, Kambiz N.; Tierney, Travis

    2015-01-01

    Deep brain stimulation (DBS) surgery, targeting various regions of the brain such as the basal ganglia, thalamus, and subthalamic regions, is an effective treatment for several movement disorders that have failed to respond to medication. Recent progress in the field of DBS surgery has begun to extend the application of this surgical technique to other conditions as diverse as morbid obesity, depression and obsessive compulsive disorder. Despite these expanding indications, little is known about the underlying physiological mechanisms that facilitate the beneficial effects of DBS surgery. One approach to this question is to perform gene expression analysis in neurons that receive the electrical stimulation. Previous studies have shown that neurogenesis in the rat dentate gyrus is elicited in DBS targeting of the anterior nucleus of the thalamus1. DBS surgery targeting the ATN is used widely for treatment refractory epilepsy. It is thus of much interest for us to explore the transcriptional changes induced by electrically stimulating the ATN. In this manuscript, we describe our methodologies for stereotactically-guided DBS surgery targeting the ATN in adult male Wistar rats. We also discuss the subsequent steps for tissue dissection, RNA isolation, cDNA preparation and quantitative RT-PCR for measuring gene expression changes. This method could be applied and modified for stimulating the basal ganglia and other regions of the brain commonly clinically targeted. The gene expression study described here assumes a candidate target gene approach for discovering molecular players that could be directing the mechanism for DBS. PMID:25867749

  12. Encoding of sequence boundaries in the subthalamic nucleus of patients with Parkinson's disease.

    PubMed

    Herrojo Ruiz, María; Rusconi, Marco; Brücke, Christof; Haynes, John-Dylan; Schönecker, Thomas; Kühn, Andrea A

    2014-10-01

    Sequential behaviour is widespread not only in humans but also in animals, ranging in different degrees of complexity from locomotion to birdsong or music performance. The capacity to learn new motor sequences relies on the integrity of basal ganglia-cortical loops. In Parkinson's disease the execution of habitual action sequences as well as the acquisition of novel sequences is impaired partly due to a deficiency in being able to generate internal cues to trigger movement sequences. In addition, patients suffering from Parkinson's disease have difficulty initiating or terminating a self-paced sequence of actions. Direct recordings from the basal ganglia in these patients show an increased level of beta (14-30 Hz) band oscillatory activity associated with impairment in movement initiation. In this framework, the current study aims to evaluate in patients with Parkinson's disease the neuronal activity in the subthalamic nucleus related to the encoding of sequence boundaries during the explicit learning of sensorimotor sequences. We recorded local field potential activity from the subthalamic nucleus of 12 patients who underwent deep brain stimulation for the treatment of advanced Parkinson's disease, while the patients in their usual medicated state practiced sequences of finger movements on a digital piano with corresponding auditory feedback. Our results demonstrate that variability in performance during an early phase of sequence acquisition correlates across patients with changes in the pattern of subthalamic beta-band oscillations; specifically, an anticipatory suppression of beta-band activity at sequence boundaries is linked to better performance. By contrast, a more compromised performance is related to attenuation of beta-band activity before within-sequence elements. Moreover, multivariate pattern classification analysis reveals that differential information about boundaries and within-sequence elements can be decoded at least 100 ms before the keystroke

  13. A three-dimensional histological atlas of the human basal ganglia. II. Atlas deformation strategy and evaluation in deep brain stimulation for Parkinson disease.

    PubMed

    Bardinet, Eric; Bhattacharjee, Manik; Dormont, Didier; Pidoux, Bernard; Malandain, Grégoire; Schüpbach, Michael; Ayache, Nicholas; Cornu, Philippe; Agid, Yves; Yelnik, Jérôme

    2009-02-01

    The localization of any given target in the brain has become a challenging issue because of the increased use of deep brain stimulation to treat Parkinson disease, dystonia, and nonmotor diseases (for example, Tourette syndrome, obsessive compulsive disorders, and depression). The aim of this study was to develop an automated method of adapting an atlas of the human basal ganglia to the brains of individual patients. Magnetic resonance images of the brain specimen were obtained before extraction from the skull and histological processing. Adaptation of the atlas to individual patient anatomy was performed by reshaping the atlas MR images to the images obtained in the individual patient using a hierarchical registration applied to a region of interest centered on the basal ganglia, and then applying the reshaping matrix to the atlas surfaces. Results were evaluated by direct visual inspection of the structures visible on MR images and atlas anatomy, by comparison with electrophysiological intraoperative data, and with previous atlas studies in patients with Parkinson disease. The method was both robust and accurate, never failing to provide an anatomically reliable atlas to patient registration. The registration obtained did not exceed a 1-mm mismatch with the electrophysiological signatures in the region of the subthalamic nucleus. This registration method applied to the basal ganglia atlas forms a powerful and reliable method for determining deep brain stimulation targets within the basal ganglia of individual patients.

  14. Deep brain and cortical stimulation for epilepsy.

    PubMed

    Sprengers, Mathieu; Vonck, Kristl; Carrette, Evelien; Marson, Anthony G; Boon, Paul

    2017-07-18

    Despite optimal medical treatment, including epilepsy surgery, many epilepsy patients have uncontrolled seizures. Since the 1970s interest has grown in invasive intracranial neurostimulation as a treatment for these patients. Intracranial stimulation includes both deep brain stimulation (DBS) (stimulation through depth electrodes) and cortical stimulation (subdural electrodes). This is an updated version of a previous Cochrane review published in 2014. To assess the efficacy, safety and tolerability of DBS and cortical stimulation for refractory epilepsy based on randomized controlled trials (RCTs). We searched the Cochrane Epilepsy Group Specialized Register on 29 September 2015, but it was not necessary to update this search, because records in the Specialized Register are included in CENTRAL. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2016, Issue 11, 5 November 2016), PubMed (5 November 2016), ClinicalTrials.gov (5 November 2016), the WHO International Clinical Trials Registry Platform ICTRP (5 November 2016) and reference lists of retrieved articles. We also contacted device manufacturers and other researchers in the field. No language restrictions were imposed. RCTs comparing deep brain or cortical stimulation versus sham stimulation, resective surgery, further treatment with antiepileptic drugs or other neurostimulation treatments (including vagus nerve stimulation). Four review authors independently selected trials for inclusion. Two review authors independently extracted the relevant data and assessed trial quality and overall quality of evidence. The outcomes investigated were seizure freedom, responder rate, percentage seizure frequency reduction, adverse events, neuropsychological outcome and quality of life. If additional data were needed, the study investigators were contacted. Results were analysed and reported separately for different intracranial targets for reasons of clinical heterogeneity

  15. The human subthalamic nucleus encodes the subjective value of reward and the cost of effort during decision-making.

    PubMed

    Zénon, Alexandre; Duclos, Yann; Carron, Romain; Witjas, Tatiana; Baunez, Christelle; Régis, Jean; Azulay, Jean-Philippe; Brown, Peter; Eusebio, Alexandre

    2016-06-01

    Adaptive behaviour entails the capacity to select actions as a function of their energy cost and expected value and the disruption of this faculty is now viewed as a possible cause of the symptoms of Parkinson's disease. Indirect evidence points to the involvement of the subthalamic nucleus-the most common target for deep brain stimulation in Parkinson's disease-in cost-benefit computation. However, this putative function appears at odds with the current view that the subthalamic nucleus is important for adjusting behaviour to conflict. Here we tested these contrasting hypotheses by recording the neuronal activity of the subthalamic nucleus of patients with Parkinson's disease during an effort-based decision task. Local field potentials were recorded from the subthalamic nucleus of 12 patients with advanced Parkinson's disease (mean age 63.8 years ± 6.8; mean disease duration 9.4 years ± 2.5) both OFF and ON levodopa while they had to decide whether to engage in an effort task based on the level of effort required and the value of the reward promised in return. The data were analysed using generalized linear mixed models and cluster-based permutation methods. Behaviourally, the probability of trial acceptance increased with the reward value and decreased with the required effort level. Dopamine replacement therapy increased the rate of acceptance for efforts associated with low rewards. When recording the subthalamic nucleus activity, we found a clear neural response to both reward and effort cues in the 1-10 Hz range. In addition these responses were informative of the subjective value of reward and level of effort rather than their actual quantities, such that they were predictive of the participant's decisions. OFF levodopa, this link with acceptance was weakened. Finally, we found that these responses did not index conflict, as they did not vary as a function of the distance from indifference in the acceptance decision. These findings show that low

  16. The human subthalamic nucleus encodes the subjective value of reward and the cost of effort during decision-making

    PubMed Central

    Zénon, Alexandre; Duclos, Yann; Carron, Romain; Witjas, Tatiana; Baunez, Christelle; Régis, Jean; Azulay, Jean-Philippe; Brown, Peter; Eusebio, Alexandre

    2016-01-01

    Adaptive behaviour entails the capacity to select actions as a function of their energy cost and expected value and the disruption of this faculty is now viewed as a possible cause of the symptoms of Parkinson’s disease. Indirect evidence points to the involvement of the subthalamic nucleus—the most common target for deep brain stimulation in Parkinson’s disease—in cost-benefit computation. However, this putative function appears at odds with the current view that the subthalamic nucleus is important for adjusting behaviour to conflict. Here we tested these contrasting hypotheses by recording the neuronal activity of the subthalamic nucleus of patients with Parkinson’s disease during an effort-based decision task. Local field potentials were recorded from the subthalamic nucleus of 12 patients with advanced Parkinson’s disease (mean age 63.8 years ± 6.8; mean disease duration 9.4 years ± 2.5) both OFF and ON levodopa while they had to decide whether to engage in an effort task based on the level of effort required and the value of the reward promised in return. The data were analysed using generalized linear mixed models and cluster-based permutation methods. Behaviourally, the probability of trial acceptance increased with the reward value and decreased with the required effort level. Dopamine replacement therapy increased the rate of acceptance for efforts associated with low rewards. When recording the subthalamic nucleus activity, we found a clear neural response to both reward and effort cues in the 1–10 Hz range. In addition these responses were informative of the subjective value of reward and level of effort rather than their actual quantities, such that they were predictive of the participant’s decisions. OFF levodopa, this link with acceptance was weakened. Finally, we found that these responses did not index conflict, as they did not vary as a function of the distance from indifference in the acceptance decision. These findings show

  17. Movement-related frequency modulation of beta oscillatory activity in the human subthalamic nucleus.

    PubMed

    Foffani, G; Bianchi, A M; Baselli, G; Priori, A

    2005-10-15

    Event-related changes of brain electrical rhythms are typically analysed as amplitude modulations of local field potential (LFP) oscillations, like radio amplitude modulation broadcasting. In telecommunications, frequency modulation (FM) is less susceptible to interference than amplitude modulation (AM) and is therefore preferred for high-fidelity transmissions. Here we hypothesized that LFP rhythms detected from deep brain stimulation (DBS) electrodes implanted in the subthalamic nucleus (STN) in patients with Parkinson's disease could represent movement-related activity not only in AM but also in FM. By combining adaptive autoregressive identification with spectral power decomposition, we were able to show that FM of low-beta (13-20 Hz) and high-beta (20-35 Hz) rhythms significantly contributes to the involvement of the human STN in movement preparation, execution and recovery, and that the FM patterns are regulated by the dopamine levels in the system. Movement-related FM of beta oscillatory activity in the human subthalamic nucleus therefore provides a novel informational domain for rhythm-based pathophysiological models of cortico-basal ganglia processing.

  18. Movement-related frequency modulation of beta oscillatory activity in the human subthalamic nucleus

    PubMed Central

    Foffani, G; Bianchi, AM; Baselli, G; Priori, A

    2005-01-01

    Event-related changes of brain electrical rhythms are typically analysed as amplitude modulations of local field potential (LFP) oscillations, like radio amplitude modulation broadcasting. In telecommunications, frequency modulation (FM) is less susceptible to interference than amplitude modulation (AM) and is therefore preferred for high-fidelity transmissions. Here we hypothesized that LFP rhythms detected from deep brain stimulation (DBS) electrodes implanted in the subthalamic nucleus (STN) in patients with Parkinson's disease could represent movement-related activity not only in AM but also in FM. By combining adaptive autoregressive identification with spectral power decomposition, we were able to show that FM of low-beta (13–20 Hz) and high-beta (20–35 Hz) rhythms significantly contributes to the involvement of the human STN in movement preparation, execution and recovery, and that the FM patterns are regulated by the dopamine levels in the system. Movement-related FM of beta oscillatory activity in the human subthalamic nucleus therefore provides a novel informational domain for rhythm-based pathophysiological models of cortico-basal ganglia processing. PMID:16123109

  19. Movement-related modulation of neural activity in human basal ganglia and its L-DOPA dependency: recordings from deep brain stimulation electrodes in patients with Parkinson's disease.

    PubMed

    Priori, A; Foffani, G; Pesenti, A; Bianchi, A; Chiesa, V; Baselli, G; Caputo, E; Tamma, F; Rampini, P; Egidi, M; Locatelli, M; Barbieri, S; Scarlato, G

    2002-09-01

    Through electrodes implanted for deep brain stimulation in three patients (5 sides) with Parkinson's disease, we recorded the electrical activity from the human basal ganglia before, during and after voluntary contralateral finger movements, before and after L-DOPA. We analysed the movement-related spectral changes in the electroencephalographic signal from the subthalamic nucleus (STN) and from the internal globus pallidus (GPi). Before, during and after voluntary movements, signals arising from the human basal ganglia contained two main frequencies: a high beta (around 26 Hz), and a low beta (around 18 Hz). The high beta (around 26 Hz) power decreased in the STN and GPi, whereas the low beta (around 18 Hz) power decrease was consistently found only in the GPi. Both frequencies changed their power with a specific temporal modulation related to the different movement phases. L-DOPA specifically and selectively influenced the spectral power changes in these two signal bands.

  20. Assessment of individual cognitive changes after deep brain stimulation surgery in Parkinson's disease using the Neuropsychological Test Battery Vienna short version.

    PubMed

    Foki, Thomas; Hitzl, Daniela; Pirker, Walter; Novak, Klaus; Pusswald, Gisela; Auff, Eduard; Lehrner, Johann

    2017-02-07

    Long-term therapy of Parkinson's disease with L‑DOPA is associated with a high risk of developing motor fluctuations and dyskinesia. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) can improve these motor complications. Although the positive effect on motor symptoms has been proven, postoperative cognitive decline has been documented. To tackle the impact of DBS on cognition, 18 DBS patients were compared to 25 best medically treated Parkinson's patients, 24 patients with mild cognitive impairment (MCI) and 12 healthy controls using the Neuropsychological Test Battery Vienna short version (NTBV-short) for cognitive outcome 12 months after the first examination. Reliable change index methodology was used. Roughly 10% of DBS patients showed cognitive decline mainly affecting the domains attention and executive functioning (phonemic fluency). Further research is needed to identify the mechanisms that lead to improvement or deterioration of cognitive functions in individual cases.

  1. Supporting clinical decision making during deep brain stimulation surgery by means of a stochastic dynamical model

    NASA Astrophysics Data System (ADS)

    Karamintziou, Sofia D.; Tsirogiannis, George L.; Stathis, Pantelis G.; Tagaris, George A.; Boviatsis, Efstathios J.; Sakas, Damianos E.; Nikita, Konstantina S.

    2014-10-01

    Objective. During deep brain stimulation (DBS) surgery for the treatment of advanced Parkinson's disease (PD), microelectrode recording (MER) in conjunction with functional stimulation techniques are commonly applied for accurate electrode implantation. However, the development of automatic methods for clinical decision making has to date been characterized by the absence of a robust single-biomarker approach. Moreover, it has only been restricted to the framework of MER without encompassing intraoperative macrostimulation. Here, we propose an integrated series of novel single-biomarker approaches applicable to the entire electrophysiological procedure by means of a stochastic dynamical model. Approach. The methods are applied to MER data pertinent to ten DBS procedures. Considering the presence of measurement noise, we initially employ a multivariate phase synchronization index for automatic delineation of the functional boundaries of the subthalamic nucleus (STN) and determination of the acceptable MER trajectories. By introducing the index into a nonlinear stochastic model, appropriately fitted to pre-selected MERs, we simulate the neuronal response to periodic stimuli (130 Hz), and examine the Lyapunov exponent as an indirect indicator of the clinical effectiveness yielded by stimulation at the corresponding sites. Main results. Compared with the gold-standard dataset of annotations made intraoperatively by clinical experts, the STN detection methodology demonstrates a false negative rate of 4.8% and a false positive rate of 0%, across all trajectories. Site eligibility for implantation of the DBS electrode, as implicitly determined through the Lyapunov exponent of the proposed stochastic model, displays a sensitivity of 71.43%. Significance. The suggested comprehensive method exhibits remarkable performance in automatically determining both the acceptable MER trajectories and the optimal stimulation sites, thereby having the potential to accelerate precise

  2. Tissue Response to Deep Brain Stimulation and Microlesion: A Comparative Study

    PubMed Central

    Baradaran‐Shoraka, Massoud; Reynolds, Brent A.; Okun, Michael S.

    2016-01-01

    Objectives Deep brain stimulation (DBS) is used for a variety of movement disorders, including Parkinson's disease. There are several theories regarding the biology and mechanisms of action of DBS. Previously, we observed an up‐regulation of neural progenitor cell proliferation in post‐mortem tissue suggesting that DBS can influence cellular plasticity in regions beyond the site of stimulation. We wanted to support these observations and investigate the relationship if any, between DBS, neural progenitor cells, and microglia. Methods We used naïve rats in this study for DBS electrode implantation, stimulation, and microlesions. We used immunohistochemistry techniques for labeling microglial and progenitor cells, and fluorescence microscopy for viewing and quantification of labeled cells. Results We present data that demonstrates a reciprocal relationship of microglia and neural precursor cells in the presence of acute high frequency stimulation. In our hands, stimulated animals demonstrate significantly lower numbers of activated microglia (p = 0.026) when compared to microlesion and sham animals. The subthalamic region surrounding the DBS stimulating electrode reveals a significant increase in the number of neural precursor cells expressing cell cycle markers, plasticity and precursor cell markers (Ki67; p = 0.0013, MCM2; p = 0.0002). Interpretation We conclude that in this animal model, acute DBS results in modest local progenitor cell proliferation and influenced the total number of activated microglia. This could be of clinical significance in patients with PD, as it is thought to progress via neuroinflammatory processes involving microglia, cytokines, and the complement system. Further studies are required to comprehend the behavior of microglia in different activation states and their ability to regulate adult neurogenesis under physiologic and pathologic conditions. PMID:27018335

  3. Role of electrode design on the volume of tissue activated during deep brain stimulation.

    PubMed

    Butson, Christopher R; McIntyre, Cameron C

    2006-03-01

    Deep brain stimulation (DBS) is an established clinical treatment for a range of neurological disorders. Depending on the disease state of the patient, different anatomical structures such as the ventral intermediate nucleus of the thalamus (VIM), the subthalamic nucleus or the globus pallidus are targeted for stimulation. However, the same electrode design is currently used in nearly all DBS applications, even though substantial morphological and anatomical differences exist between the various target nuclei. The fundamental goal of this study was to develop a theoretical understanding of the impact of changes in the DBS electrode contact geometry on the volume of tissue activated (VTA) during stimulation. Finite element models of the electrodes and surrounding medium were coupled to cable models of myelinated axons to predict the VTA as a function of stimulation parameter settings and electrode design. Clinical DBS electrodes have cylindrical contacts 1.27 mm in diameter (d) and 1.5 mm in height (h). Our results show that changes in contact height and diameter can substantially modulate the size and shape of the VTA, even when contact surface area is preserved. Electrode designs with a low aspect ratio (d/h) maximize the VTA by providing greater spread of the stimulation parallel to the electrode shaft without sacrificing lateral spread. The results of this study provide the foundation necessary to customize electrode design and VTA shape for specific anatomical targets, and an example is presented for the VIM. A range of opportunities exist to engineer DBS systems to maximize stimulation of the target area while minimizing stimulation of non-target areas. Therefore, it may be possible to improve therapeutic benefit and minimize side effects from DBS with the design of target-specific electrodes.

  4. Effect of low-frequency deep brain stimulation on sensory thresholds in Parkinson's disease.

    PubMed

    Belasen, Abigail; Rizvi, Khizer; Gee, Lucy E; Yeung, Philip; Prusik, Julia; Ramirez-Zamora, Adolfo; Hanspal, Era; Paiva, Priscilla; Durphy, Jennifer; Argoff, Charles E; Pilitsis, Julie G

    2017-02-01

    OBJECTIVE Chronic pain is a major distressing symptom of Parkinson's disease (PD) that is often undertreated. Subthalamic nucleus (STN) deep brain stimulation (DBS) delivers high-frequency stimulation (HFS) to patients with PD and has been effective in pain relief in a subset of these patients. However, up to 74% of patients develop new pain concerns while receiving STN DBS. Here the authors explore whether altering the frequency of STN DBS changes pain perception as measured through quantitative sensory testing (QST). METHODS Using QST, the authors measured thermal and mechanical detection and pain thresholds in 19 patients undergoing DBS via HFS, low-frequency stimulation (LFS), and off conditions in a randomized order. Testing was performed in the region of the body with the most pain and in the lower back in patients without chronic pain. RESULTS In the patients with chronic pain, LFS significantly reduced heat detection thresholds as compared with thresholds following HFS (p = 0.029) and in the off state (p = 0.010). Moreover, LFS resulted in increased detection thresholds for mechanical pressure (p = 0.020) and vibration (p = 0.040) compared with these thresholds following HFS. Neither LFS nor HFS led to changes in other mechanical thresholds. In patients without chronic pain, LFS significantly increased mechanical pain thresholds in response to the 40-g pinprick compared with thresholds following HFS (p = 0.032). CONCLUSIONS Recent literature has suggested that STN LFS can be useful in treating nonmotor symptoms of PD. Here the authors demonstrated that LFS modulates thermal and mechanical detection to a greater extent than HFS. Low-frequency stimulation is an innovative means of modulating chronic pain in PD patients receiving STN DBS. The authors suggest that STN LFS may be a future option to consider when treating Parkinson's patients in whom pain remains the predominant complaint.

  5. Facilitating effects of deep brain stimulation on feedback learning in Parkinson's disease.

    PubMed

    Meissner, Sarah Nadine; Südmeyer, Martin; Keitel, Ariane; Pollok, Bettina; Bellebaum, Christian

    2016-10-15

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) provides an effective treatment for Parkinson's disease (PD) motor symptoms. However, findings of effects on cognitive function such as feedback learning remain controversial and rare. The aim of the present study was to gain a better understanding of cognitive alterations associated with STN-DBS. Therefore, we investigated effects of STN-DBS on active and observational feedback learning in PD. 18 PD patients with STN-DBS and 18 matched healthy controls completed active and observational feedback learning tasks. Patients were investigated ON and OFF STN-DBS. Tasks consisted of learning (with feedback) and test phases (without feedback). STN-DBS improved active learning during feedback trials and PD patients ON (but not OFF) STN-DBS showed comparable performance patterns as healthy controls. No STN-DBS effect was found when assessing performance during active test trials without feedback. In this case, however, STN-DBS effects were found to depend on symptom severity. While more impaired patients benefited from STN-DBS, stimulation had no facilitating effect on patients with less severe symptoms. Along similar lines, the severity of motor symptoms tended to be significantly correlated with differences in active test performance due to STN-DBS. For observational feedback learning, there was a tendency for a positive STN-DBS effect with patients reaching the performance level of healthy controls only ON STN-DBS. The present data suggest that STN-DBS facilitates active feedback learning in PD patients. Furthermore, they provide first evidence that STN-DBS might not only affect learning from own but also from observed actions and outcomes.

  6. A Fuzzy Inference System for Closed-Loop Deep Brain Stimulation in Parkinson's Disease.

    PubMed

    Camara, Carmen; Warwick, Kevin; Bruña, Ricardo; Aziz, Tipu; del Pozo, Francisco; Maestú, Fernando

    2015-11-01

    Parkinsons disease is a complex neurodegenerative disorder for which patients present many symptoms, tremor being the main one. In advanced stages of the disease, Deep Brain Stimulation is a generalized therapy which can significantly improve the motor symptoms. However despite its beneficial effects on treating the symptomatology, the technique can be improved. One of its main limitations is that the parameters are fixed, and the stimulation is provided uninterruptedly, not taking into account any fluctuation in the patients state. A closed-loop system which provides stimulation by demand would adjust the stimulation to the variations in the state of the patient, stimulating only when it is necessary. It would not only perform a more intelligent stimulation, capable of adapting to the changes in real time, but also extending the devices battery life, thereby avoiding surgical interventions. In this work we design a tool that learns to recognize the principal symptom of Parkinsons disease and particularly the tremor. The goal of the designed system is to detect the moments the patient is suffering from a tremor episode and consequently to decide whether stimulation is needed or not. For that, local field potentials were recorded in the subthalamic nucleus of ten Parkinsonian patients, who were diagnosed with tremor-dominant Parkinsons disease and who underwent surgery for the implantation of a neurostimulator. Electromyographic activity in the forearm was simultaneously recorded, and the relation between both signals was evaluated using two different synchronization measures. The results of evaluating the synchronization indexes on each moment represent the inputs to the designed system. Finally, a fuzzy inference system was applied with the goal of identifying tremor episodes. Results are favourable, reaching accuracies of higher 98.7% in 70% of the patients.

  7. "Asleep" Deep Brain Stimulation Surgery: A Critical Review of the Literature.

    PubMed

    Chen, Tsinsue; Mirzadeh, Zaman; Ponce, Francisco A

    2017-09-01

    Although performing deep brain stimulation (DBS) with the patient under general anesthesia without microelectrode recording (MER) or intraoperative test stimulation (ITS) for movement disorders ("asleep" DBS) has become increasingly popular, its feasibility is based on the untested assumption that stereotactic accuracy correlates with positive clinical outcomes. To investigate outcomes after asleep DBS without MER or neurophysiological testing, we reviewed the medical literature on the topic. We searched PubMed to identify all studies reporting clinical outcomes for patients who underwent DBS without MER or ITS for Parkinson disease (PD) or essential tremor (ET). We identified 9 studies with level 3b (n = 3) or level 4 evidence (n = 6). Eight PD studies (220 patients) reported asleep placement of 431 electrodes (341 subthalamic nucleus, 90 globus pallidus interna). Unified Parkinson Disease Rating Scale motor examination-III scores for 208 patients demonstrated significant improvement (40.2%-65%) at 6-12 months. The levodopa equivalent daily dose for 115 patients was significantly reduced (14%-49.3%) at 6-12 months in 103 patients. Two studies with a comparison cohort undergoing "awake" DBS with MER found no differences in postoperative Unified Parkinson Disease Rating Scale-III improvement or levodopa equivalent daily dose reduction. One study of asleep DBS for ET found no difference in functional outcomes between 17 patients undergoing asleep ventral intermediate nucleus DBS and 40 patients undergoing awake placement with ITS. Initial evidence suggests that asleep DBS can be performed safely for PD and ET with good clinical outcomes. Long-term follow-up, larger cohorts, and double-armed studies are needed to validate these initial results. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Body weight gain in patients with bilateral deep brain stimulation for dystonia.

    PubMed

    Wolf, Marc E; Capelle, Hans-Holger; Lütjens, Götz; Ebert, Anne D; Hennerici, Michael G; Krauss, Joachim K; Blahak, Christian

    2016-03-01

    In patients with Parkinson's disease, significant weight gain following chronic deep brain stimulation (DBS) has been reported. Recently, relevant weight gain could be demonstrated also following subthalamic nucleus DBS in patients with primary cervical dystonia. Prospective analyses of body weight changes following DBS in patients with dystonia, however, have not been published so far. We aimed to analyse the changes of body weight following DBS in patients with dystonia. The body mass index (BMI) of 17 consecutive patients with segmental or generalised dystonia (mean age 54.6 ± 16.1 years) treated with bilateral DBS of the globus pallidus internus (GPi) (n = 14) or the thalamic ventral intermediate nucleus (n = 3) was measured preoperatively (pre-OP) and at three follow-up (FU) time points post-DBS surgery (FU1 = 7 months, FU2 = 17 months, FU3 = 72 months). All patients benefited from marked improvement in their dystonia. The mean BMI pre-OP (SD) was 22.5 (±3.7) kg/m(2) and increased stepwise to 24.0 (±3.3) kg/m(2) at FU1, 24.4 (±3.7) kg/m(2) at FU2 and 24.9 (±3.7) kg/m(2) at FU3 (p < 0.05 at all three FUs compared to pre-OP). Relative BMI increase and improvement of dystonia were correlated (p = 0.025). Chronic bilateral GPi DBS in patients with dystonia is associated with significant body weight gain, in particular during the first 6 months post-OP. This probably is a result of improvement of dystonic motor symptoms and recovery of eating dysfunction rather than a target-specific phenomenon.

  9. Quantitative analysis of axonal fiber activation evoked by deep brain stimulation via activation density heat maps

    PubMed Central

    Hartmann, Christian J.; Chaturvedi, Ashutosh; Lujan, J. Luis

    2015-01-01

    Background: Cortical modulation is likely to be involved in the various therapeutic effects of deep brain stimulation (DBS). However, it is currently difficult to predict the changes of cortical modulation during clinical adjustment of DBS. Therefore, we present a novel quantitative approach to estimate anatomical regions of DBS-evoked cortical modulation. Methods: Four different models of the subthalamic nucleus (STN) DBS were created to represent variable electrode placements (model I: dorsal border of the posterolateral STN; model II: central posterolateral STN; model III: central anteromedial STN; model IV: dorsal border of the anteromedial STN). Axonal fibers of passage near each electrode location were reconstructed using probabilistic tractography and modeled using multi-compartment cable models. Stimulation-evoked activation of local axon fibers and corresponding cortical projections were modeled and quantified. Results: Stimulation at the border of the STN (models I and IV) led to a higher degree of fiber activation and associated cortical modulation than stimulation deeply inside the STN (models II and III). A posterolateral target (models I and II) was highly connected to cortical areas representing motor function. Additionally, model I was also associated with strong activation of fibers projecting to the cerebellum. Finally, models III and IV showed a dorsoventral difference of preferentially targeted prefrontal areas (models III: middle frontal gyrus; model IV: inferior frontal gyrus). Discussion: The method described herein allows characterization of cortical modulation across different electrode placements and stimulation parameters. Furthermore, knowledge of anatomical distribution of stimulation-evoked activation targeting cortical regions may help predict efficacy and potential side effects, and therefore can be used to improve the therapeutic effectiveness of individual adjustments in DBS patients. PMID:25713510

  10. Understanding the impact of deep brain stimulation on ambulatory activity in advanced Parkinson's disease.

    PubMed

    Rochester, Lynn; Chastin, Sebastien Francois Martin; Lord, Sue; Baker, Katherine; Burn, David John

    2012-06-01

    Whilst deep brain stimulation of the subthalamic nucleus (DBS-STN) improves the motor symptoms of Parkinson's disease (PD), its effect on daily activity is unknown. We aimed to quantify changes in ambulatory activity following DBS-STN in advanced PD using novel accelerometry based measures that describe changes to the volume and pattern of walking. Seventeen participants with advanced PD were measured over a 7-day period using an activPAL (™) activity monitor. Data were collected 6 weeks before and 6 months after surgery and included measures that describe the volume and pattern of ambulatory activity (number of steps per day, accumulation, diversity and variability of walking time), alongside standard measures for disease severity, freezing of gait, gait speed, and extended activities of daily living. Activity outcomes were compared pre- and 6 months post-surgery using linear mixed models and correlated with standard outcomes. The results of this study are despite significant improvements in motor symptoms after surgery, the volume of ambulatory activity (total number of steps per day) did not change (P = 0.468). However, significant increases in length and variability of walking bouts emerged, suggesting improvements in diversity and flexibility of walking patterns. Motor severity and extended activities of daily living scores were significantly correlated with walking bout variability but not with volume of walking. Thus, the conclusions are reduction in motor symptom severity after DBS-STN translated into selective improvements in daily activity. Novel measures derived from accelerometry provide a discrete measure of performance and allow closer interpretation of the impact of DBS-STN on real-world activity.

  11. Quantifying the Neural Elements Activated and Inhibited by Globus Pallidus Deep Brain Stimulation

    PubMed Central

    Johnson, Matthew D.; McIntyre, Cameron C.

    2008-01-01

    Deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) is an effective therapy option for controlling the motor symptoms of medication-refractory Parkinson's disease and dystonia. Despite the clinical successes of GPi DBS, the precise therapeutic mechanisms are unclear and questions remain on the optimal electrode placement and stimulation parameter selection strategies. In this study, we developed a three-dimensional computational model of GPi-DBS in nonhuman primates to investigate how membrane channel dynamics, synaptic inputs, and axonal collateralization contribute to the neural responses generated during stimulation. We focused our analysis on three general neural elements that surround GPi-DBS electrodes: GPi somatodendritic segments, GPi efferent axons, and globus pallidus pars externa (GPe) fibers of passage. During high-frequency electrical stimulation (136 Hz), somatic activity in the GPi showed interpulse excitatory phases at 1–3 and 4–5.5 ms. When including stimulation-induced GABAA and AMPA receptor dynamics into the model, the somatic firing patterns continued to be entrained to the stimulation, but the overall firing rate was reduced (78.7 to 25.0 Hz, P < 0.001). In contrast, axonal output from GPi neurons remained largely time-locked to each pulse of the stimulation train. Similar entrainment was also observed in GPe efferents, a majority of which have been shown to project through GPi en route to the subthalamic nucleus. The models suggest that pallidal DBS may have broader network effects than previously realized and the modes of therapy may depend on the relative proportion of GPi and/or GPe efferents that are directly affected by the stimulation. PMID:18768645

  12. Comparison of General and Local Anesthesia for Deep Brain Stimulator Insertion: A Systematic Review.

    PubMed

    Sheshadri, Veena; Rowland, Nathan C; Mehta, Jigesh; Englesakis, Marina; Manninen, Pirjo; Venkatraghavan, Lashmi

    2017-09-18

    Subthalamic nucleus deep brain stimulation (STN-DBS) has become a standard treatment for many patients with Parkinson's disease (PD). The reported clinical outcome measures for procedures done under general anesthesia (GA) compared to traditional local anesthetic (LA) technique are quite heterogeneous and difficult to compare. The aim of this systematic review and metaanalysis was to determine whether the clinical outcome after STN-DBS insertion under GA is comparable to that under LA in patients with Parkinson's disease. The databases of Medline Embase, Cochrane library and Pubmed were searched for eligible studies (human trials, English language, published between 1946 and January of 2016). The primary outcome of this study was to assess the postoperative improvement in the symptoms, evaluated using either Unified Parkinson's Disease Rating Scale (UPDRS) scores or levodopa equivalent dosage (LEDD) requirement. The literature searches yielded 395 citations and six retrospective cohort studies with a sample size of 455 (194 in GA and 261 in LA) were included in the analysis. Regarding the clinical outcomes, there were no significant differences in the postoperative Unified Parkinson's disease rating scale and levodopa equivalent drug dosage between the GA and the LA groups. Similarly, the adverse events and target accuracy were also comparable between the groups. This systematic review and meta-analysis shows that currently there is no good quality data to suggest equivalence of GA to LA during STN-DBS insertion in patients with PD, with some factors trending towards LA. There is a need for a prospective randomized control trial to validate our results.

  13. Postoperative neuroimaging analysis of DRT deep brain stimulation revision surgery for complicated essential tremor.

    PubMed

    Coenen, Volker Arnd; Varkuti, Balint; Parpaley, Yaroslav; Skodda, Sabine; Prokop, Thomas; Urbach, Horst; Li, Meng; Reinacher, Peter Christoph

    2017-05-01

    We report a patient who received conventional bilateral deep brain stimulation of the ventral intermediate nucleus of thalamus (Vim) for the treatment of medication refractory essential tremor (ET). After initial beneficial effects, therapeutic efficacy was lost due to a loss of control of his proximal trunkal and extremity tremor. The patient received successful diffusion tensor magnetic resonance imaging fiber tractographic (DTI FT)-assisted DBS revision surgery targeting the dentato-rubro-thalamic tract (DRT) in the subthalamic region (STR). To report the concept of DTI FT-assisted DRT DBS revision surgery for ET and to show sophisticated postoperative neuroimaging analysis explaining improved symptom control. Analysis was based on preoperative DTI sequences and postoperative helical computed tomography (hCT). Leads, stimulation fields, and fibers were reconstructed using commercial software systems (Elements, Brainlab AG, Feldkirchen, Germany; GUIDE XT, Boston Scientific Corp., Boston, MA, USA). The patient showed immediate and sustained tremor improvement after DTI FT-assisted revision surgery. Analysis of the two implantations (electrode positions in both instances) revealed a lateral and posterior shift in the pattern of modulation of the cortical fiber pathway projection after revision surgery as compared to initial implantation, explaining a more efficacious stimulation. Our work underpins a possible superiority of direct targeting approaches using advanced neuroimaging technologies to perform personalized DBS surgery. The evaluation of DBS electrode positions with the herein-described neuroimaging simulation technologies will likely improve targeting and revision strategies. Direct targeting with DTI FT-assisted approaches in a variety of indications is the focus of our ongoing research.

  14. Coordinate-based lead location does not predict Parkinson's disease deep brain stimulation outcome.

    PubMed

    Nestor, Kelsey A; Jones, Jacob D; Butson, Christopher R; Morishita, Takashi; Jacobson, Charles E; Peace, David A; Chen, Dennis; Foote, Kelly D; Okun, Michael S

    2014-01-01

    Effective target regions for deep brain stimulation (DBS) in Parkinson's disease (PD) have been well characterized. We sought to study whether the measured Cartesian coordinates of an implanted DBS lead are predictive of motor outcome(s). We tested the hypothesis that the position and trajectory of the DBS lead relative to the mid-commissural point (MCP) are significant predictors of clinical outcomes. We expected that due to neuroanatomical variation among individuals, a simple measure of the position of the DBS lead relative to MCP (commonly used in clinical practice) may not be a reliable predictor of clinical outcomes when utilized alone. 55 PD subjects implanted with subthalamic nucleus (STN) DBS and 41 subjects implanted with globus pallidus internus (GPi) DBS were included. Lead locations in AC-PC space (x, y, z coordinates of the active contact and sagittal and coronal entry angles) measured on high-resolution CT-MRI fused images, and motor outcomes (Unified Parkinson's Disease Rating Scale) were analyzed to confirm or refute a correlation between coordinate-based lead locations and DBS motor outcomes. Coordinate-based lead locations were not a significant predictor of change in UPDRS III motor scores when comparing pre- versus post-operative values. The only potentially significant individual predictor of change in UPDRS motor scores was the antero-posterior coordinate of the GPi lead (more anterior lead locations resulted in a worse outcome), but this was only a statistical trend (p<.082). The results of the study showed that a simple measure of the position of the DBS lead relative to the MCP is not significantly correlated with PD motor outcomes, presumably because this method fails to account for individual neuroanatomical variability. However, there is broad agreement that motor outcomes depend strongly on lead location. The results suggest the need for more detailed identification of stimulation location relative to anatomical targets.

  15. An automated approach towards detecting complex behaviours in deep brain oscillations.

    PubMed

    Mace, Michael; Yousif, Nada; Naushahi, Mohammad; Abdullah-Al-Mamun, Khondaker; Wang, Shouyan; Nandi, Dipankar; Vaidyanathan, Ravi

    2014-03-15

    Extracting event-related potentials (ERPs) from neurological rhythms is of fundamental importance in neuroscience research. Standard ERP techniques typically require the associated ERP waveform to have low variance, be shape and latency invariant and require many repeated trials. Additionally, the non-ERP part of the signal needs to be sampled from an uncorrelated Gaussian process. This limits methods of analysis to quantifying simple behaviours and movements only when multi-trial data-sets are available. We introduce a method for automatically detecting events associated with complex or large-scale behaviours, where the ERP need not conform to the aforementioned requirements. The algorithm is based on the calculation of a detection contour and adaptive threshold. These are combined using logical operations to produce a binary signal indicating the presence (or absence) of an event with the associated detection parameters tuned using a multi-objective genetic algorithm. To validate the proposed methodology, deep brain signals were recorded from implanted electrodes in patients with Parkinson's disease as they participated in a large movement-based behavioural paradigm. The experiment involved bilateral recordings of local field potentials from the sub-thalamic nucleus (STN) and pedunculopontine nucleus (PPN) during an orientation task. After tuning, the algorithm is able to extract events achieving training set sensitivities and specificities of [87.5 ± 6.5, 76.7 ± 12.8, 90.0 ± 4.1] and [92.6 ± 6.3, 86.0 ± 9.0, 29.8 ± 12.3] (mean ± 1 std) for the three subjects, averaged across the four neural sites. Furthermore, the methodology has the potential for utility in real-time applications as only a single-trial ERP is required.

  16. Deep brain stimulation in early stage Parkinson's disease: operative experience from a prospective randomised clinical trial.

    PubMed

    Kahn, Elyne; D'Haese, Pierre-Francois; Dawant, Benoit; Allen, Laura; Kao, Chris; Charles, P David; Konrad, Peter

    2012-02-01

    Recent evidence suggests that deep brain stimulation of the subthalamic nucleus (STN-DBS) may have a disease modifying effect in early Parkinson's disease (PD). A randomised, prospective study is underway to determine whether STN-DBS in early PD is safe and tolerable. 15 of 30 early PD patients were randomised to receive STN-DBS implants in an institutional review board approved protocol. Operative technique, location of DBS leads and perioperative adverse events are reported. Active contact used for stimulation in these patients was compared with 47 advanced PD patients undergoing an identical procedure by the same surgeon. 14 of the 15 patients did not sustain any long term (>3 months) complications from the surgery. One subject suffered a stroke resulting in mild cognitive changes and slight right arm and face weakness. The average optimal contact used in symptomatic treatment of early PD patients was: anterior -1.1±1.7 mm, lateral 10.7±1.7 mm and superior -3.3±2.5 mm (anterior and posterior commissure coordinates). This location is statistically no different (0.77 mm, p>0.05) than the optimal contact used in the treatment of 47 advanced PD patients. The perioperative adverse events in this trial of subjects with early stage PD are comparable with those reported for STN-DBS in advanced PD. The active contact position used in early PD is not significantly different from that used in late stage disease. This is the first report of the operative experience from a randomised, surgical versus best medical therapy trial for the early treatment of PD.

  17. Role of electrode design on the volume of tissue activated during deep brain stimulation

    NASA Astrophysics Data System (ADS)

    Butson, Christopher R.; McIntyre, Cameron C.

    2006-03-01

    Deep brain stimulation (DBS) is an established clinical treatment for a range of neurological disorders. Depending on the disease state of the patient, different anatomical structures such as the ventral intermediate nucleus of the thalamus (VIM), the subthalamic nucleus or the globus pallidus are targeted for stimulation. However, the same electrode design is currently used in nearly all DBS applications, even though substantial morphological and anatomical differences exist between the various target nuclei. The fundamental goal of this study was to develop a theoretical understanding of the impact of changes in the DBS electrode contact geometry on the volume of tissue activated (VTA) during stimulation. Finite element models of the electrodes and surrounding medium were coupled to cable models of myelinated axons to predict the VTA as a function of stimulation parameter settings and electrode design. Clinical DBS electrodes have cylindrical contacts 1.27 mm in diameter (d) and 1.5 mm in height (h). Our results show that changes in contact height and diameter can substantially modulate the size and shape of the VTA, even when contact surface area is preserved. Electrode designs with a low aspect ratio (d/h) maximize the VTA by providing greater spread of the stimulation parallel to the electrode shaft without sacrificing lateral spread. The results of this study provide the foundation necessary to customize electrode design and VTA shape for specific anatomical targets, and an example is presented for the VIM. A range of opportunities exist to engineer DBS systems to maximize stimulation of the target area while minimizing stimulation of non-target areas. Therefore, it may be possible to improve therapeutic benefit and minimize side effects from DBS with the design of target-specific electrodes.

  18. Unilateral deep brain stimulation surgery in Parkinson’s disease improves ipsilateral symptoms regardless of laterality

    PubMed Central

    Shemisa, Kamal; Hass, Chris J.; Foote, Kelly D.; Okun, Michael S.; Wu, Samuel S.; Jacobson, Charles E.; Dai, Yunfeng; Oyama, Genko; Fernandez, Hubert H.

    2013-01-01

    Purpose Researchers have consistently observed in right-handed individuals across normal and disease states that the ‘dominant’ left hemisphere has greater ipsilateral control of the left side than the right hemisphere has over the right. We sought to determine whether this ipsilateral influence of the dominant hemisphere reported in Parkinson’s disease extends to treatments such as deep brain stimulation (DBS) and whether it affects outcome. We hypothesised that among Parkinson right-handers, unilateral left DBS would provide greater ipsilateral motor improvement compared with the ipsilateral motor improvement experienced on the right side. Scope A total of 73 Parkinson patients who underwent unilateral DBS of the subthalamic nucleus (STN) or globus palidus internus (GPi) participated. Left and right ‘composite scores’, were computed by separately adding all items on the left and right side from the motor section of the Unified Parkinson Disease Rating Scale. The change in the pre- and 4-month post-implantation score was the primary outcome measure. The mean motor scores improved by 4.96 ± 11.79 points (p < 0.001) post-surgery on the ipsilateral side of the DBS implantation. Regression analyses revealed that the side (left vs. right) and target (STN vs. GPi) did not significantly contribute in the effect of ipsilateral motor improvement (p = 0.3557). Conclusion While DBS on the ‘dominant’ left side failed to exert a greater ipsilateral influence compared with DBS on the non-dominant right side, significant ipsilateral motor improvements were observed after unilateral stimulation regardless of site of implantation and laterality. PMID:21856205

  19. Deep Brain Stimulation for Parkinson’s Disease: Recent Trends and Future Direction

    PubMed Central

    FUKAYA, Chikashi; YAMAMOTO, Takamitsu

    2015-01-01

    To date, deep brain stimulation (DBS) has already been performed on more than 120,000 patients worldwide and in more than 7,000 patients in Japan. However, fundamental understanding of DBS effects on the pathological neural circuitry remains insufficient. Recent studies have specifically shown the importance of cortico-striato-thalamo-cortical (CSTC) loops, which were identified as functionally and anatomically discrete units. Three main circuits exist in the CSTC loops, namely, the motor, associative, and limbic circuits. From these theoretical backgrounds, it is determined that DBS sometimes influences not only motor functions but also the cognitive and affective functions of Parkinson’s disease (PD) patients. The main targets of DBS for PD are subthalamic nucleus (STN) and globus pallidus interna (GPi). Ventralis intermedius (Vim)-DBS was found to be effective in improving tremor. However, Vim-DBS cannot sufficiently improve akinesia and rigidity. Therefore, Vim-DBS is seldom carried out for the treatment of PD. In this article, we review the present state of DBS, mainly STN-DBS and GPi-DBS, for PD. In the first part of the article, appropriate indications and practical effects established in previous studies are discussed. The findings of previous investigations on the complications caused by the surgical procedure and on the adverse events induced by DBS itself are reviewed. In the second part, we discuss target selection (GPi vs. STN) and the effect of DBS on nonmotor symptoms. In the final part, as issues that should be resolved, the suitable timing of surgery, symptoms unresponsive to DBS such as on-period axial symptoms, and the related postoperative programing of stimulation parameters, are discussed. PMID:25925761

  20. Deep brain stimulation improves movement amplitude but not hastening of repetitive finger movements.

    PubMed

    Stegemöller, Elizabeth L; Zadikoff, Cindy; Rosenow, Joshua M; Mackinnon, Colum D

    2013-09-27

    External pacing cues, dopaminergic medication, and bilateral subthalamic nucleus deep brain stimulation (STN-DBS) improve repetitive movements performed at low rates. When the pacing rate is increased to frequencies near 2 Hz and above, both external pacing cues and Parkinson's medication were shown to be ineffective at improving repetitive finger movement performance. It remains unclear if STN-DBS improves the performance of repetitive finger movements at high pacing rates. This study examined the effects of STN-DBS on the amplitude and rate of repetitive finger movement across a range of external pacing rates. Nine participants with STN-DBS (OFF and ON stimulation) and nine matched healthy adults performed repetitive index finger flexion movements paced by an acoustic tone that increased from 1.0 to 3.0 Hz. OFF stimulation, most subjects moved at rates that were substantially higher (hastening pattern) or lower (bradykinesia pattern) than the tone rate, particularly at high pacing rates. ON stimulation, movement rate improved in subjects with the bradykinesia pattern, but not in those with the hastening pattern. Overall, STN-DBS did not significantly affect movement rate. In contrast, STN-DBS significantly (p<0.05) improved movement amplitude across all pacing rates. These findings demonstrate that STN-DBS improves movement amplitude, but had no effect on the rate of movement in participants with a hastening pattern. Separately testing movement amplitude and movement rate using both high and low rate externally paced cues in the clinical environment may aid in the diagnosis and treatment of people with Parkinson's disease. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  1. What You See Is What You Get: Lead Location Within Deep Brain Structures Is Accurately Depicted by Stereotactic Magnetic Resonance Imaging.

    PubMed

    Hyam, Jonathan A; Akram, Harith; Foltynie, Thomas; Limousin, Patricia; Hariz, Marwan; Zrinzo, Ludvic

    2015-09-01

    Magnetic resonance imaging (MRI)-verified deep brain stimulation relies on the correct interpretation of stereotactic imaging documenting lead location in relation to visible anatomic target. However, it has been suggested that local signal distortion from the lead itself renders its depiction on MRI unreliable. To compare lead location on stereotactic MRI with subsequent location of its brain track after removal. Patients underwent deep brain stimulation with the use of MRI-guided and MRI-verified Leksell frame approach. Infection or suboptimal efficacy required lead removal and subsequent reimplantation by using the same technique. Postimplantation stereotactic MR images were analyzed. Lateral (x) and anteroposterior (y) distances from midcommissural point to center of the lead hypointensity were recorded at the anterior commissure-posterior commissure plane (pallidal electrode) or z = -4 (subthalamic electrode). Stereotactic MRI before the second procedure, x and y distances from the center of the visible lead track hypointensity to midcommissural point were independently recorded. Vectorial distance from center of the lead hypointensity to the center of its track was calculated. Sixteen electrode tracks were studied in 10 patients. Mean differences between lead artifact location and lead track location were: x coordinate 0.4 mm ± 0.2; y coordinate 0.6 mm ± 0.3. Mean vectorial distance was 0.7 mm ± 0.2. Stereotactic distance between lead location and subsequent brain track location on MRI was small. The mean discrepancy was approximately half the deep brain stimulation lead width. This suggests that lead hypointensity seen on postimplantation MRI is indeed an accurate representation of its real location within deep brain structures.

  2. Is deep brain stimulation a form of psychosurgery?

    PubMed

    Sachdev, Perminder

    2007-04-01

    To examine the potential for the experimental treatment of deep brain stimulation for neuropsychiatric disorders, and to debate the argument that it should be considered another form of psychosurgery. Psychosurgery is an old term with considerable pejorative connotations. It should be replaced with the more descriptive and accurate 'neurosurgery for psychiatric disorders'. Moreover, neurosurgery should reflect ablative neurosurgery, and surgery for brain stimulation should be categorised as brain stimulation rather than neurosurgery, or indeed psychosurgery. This will prevent legislative restrictions on the development of brain stimulation techniques and not tar them with the lobotomy brush.

  3. Deep Brain Stimulation for Essential Vocal Tremor: A Technical Report.

    PubMed

    Ho, Allen L; Choudhri, Omar; Sung, C Kwang; DiRenzo, Elizabeth E; Halpern, Casey H

    2015-03-01

    Essential vocal tremor (EVT) is the presence of a tremulous voice that is commonly associated with essential tremor. Patients with EVT often report a necessary increase in vocal effort that significantly worsens with stress and anxiety and can significantly impact quality of life despite optimal medical and behavioral treatment options. Deep brain stimulation (DBS) has been proposed as an effective therapy for vocal tremor, but very few studies exist in the literature that comprehensively evaluate the efficacy of DBS for specifically addressing EVT. We present a technical report on our multidisciplinary, comprehensive operative methodology for treatment of EVT with frameless, awake deep brain stimulation (DBS).

  4. Deep Brain Stimulation for Essential Vocal Tremor: A Technical Report

    PubMed Central

    Choudhri, Omar; Sung, C. Kwang; DiRenzo, Elizabeth E; Halpern, Casey H

    2015-01-01

    Essential vocal tremor (EVT) is the presence of a tremulous voice that is commonly associated with essential tremor. Patients with EVT often report a necessary increase in vocal effort that significantly worsens with stress and anxiety and can significantly impact quality of life despite optimal medical and behavioral treatment options. Deep brain stimulation (DBS) has been proposed as an effective therapy for vocal tremor, but very few studies exist in the literature that comprehensively evaluate the efficacy of DBS for specifically addressing EVT. We present a technical report on our multidisciplinary, comprehensive operative methodology for treatment of EVT with frameless, awake deep brain stimulation (DBS). PMID:26180680

  5. Stochastic Phase Resetting: A Theory for Deep Brain Stimulation

    NASA Astrophysics Data System (ADS)

    Tass, P. A.

    The basic principles of a stochastic approach to phase resetting in populations of interacting phase oscillators are presented in this article. This theory explains how synchronization and desynchronization processes are caused by a pulsatile stimulus. It is a central goal of this approach to establish a theoretical basis for the design of efficient and intelligent new deep brain stimulation techniques. Accordingly, the theory is used to design a new deep brain stimulation technique with feedback control in patients suffering from Parkinson's disease or essential tremor.

  6. Deep brain stimulation for treatment of cervical dystonia.

    PubMed

    Krauss, J K

    2007-01-01

    Pallidal deep brain stimulation is an efficient treatment option in those patients with cervical dystonia who do not benefit from conservative treatment including local botulinum toxin injections. Given the fact that other surgical treatment options such as selective peripheral denervation are available, it may be considered third-line treatment in most instances. Chronic bilateral pallidal stimulation improves dystonic posture and movements, pain caused by dystonia and disability related to dystonia. Preliminary data on longterm follow-up confirm its beneficial effect in the majority of patients. Given the frequency of cervical dystonia, pallidal deep brain stimulation will play a major role in the future.

  7. Pedunculopontine arousal system physiology - Deep brain stimulation (DBS).

    PubMed

    Garcia-Rill, Edgar; Luster, Brennon; D'Onofrio, Stasia; Mahaffey, Susan; Bisagno, Veronica; Urbano, Francisco J

    2015-11-01

    This review describes the wake/sleep symptoms present in Parkinson׳s disease, and the role of the pedunculopontine nucleus in these symptoms. The physiology of PPN cells is important not only because it is a major element of the reticular activating system, but also because it is a novel target for deep brain stimulation in the treatment of gait and postural deficits in Parkinson׳s disease. A greater understanding of the physiology of the target nuclei within the brainstem and basal ganglia, amassed over the past decades, has enabled increasingly better patient outcomes from deep brain stimulation for movement disorders.

  8. Pedunculopontine arousal system physiology – Deep brain stimulation (DBS)

    PubMed Central

    Garcia-Rill, Edgar; Luster, Brennon; D’Onofrio, Stasia; Mahaffey, Susan; Bisagno, Veronica; Urbano, Francisco J.

    2015-01-01

    This review describes the wake/sleep symptoms present in Parkinson׳s disease, and the role of the pedunculopontine nucleus in these symptoms. The physiology of PPN cells is important not only because it is a major element of the reticular activating system, but also because it is a novel target for deep brain stimulation in the treatment of gait and postural deficits in Parkinson׳s disease. A greater understanding of the physiology of the target nuclei within the brainstem and basal ganglia, amassed over the past decades, has enabled increasingly better patient outcomes from deep brain stimulation for movement disorders. PMID:26779322

  9. Subthalamic local field potentials in Parkinson's disease and isolated dystonia: An evaluation of potential biomarkers.

    PubMed

    Wang, Doris D; de Hemptinne, Coralie; Miocinovic, Svjetlana; Qasim, Salman E; Miller, Andrew M; Ostrem, Jill L; Galifianakis, Nicholas B; San Luciano, Marta; Starr, Philip A

    2016-05-01

    Local field potentials (LFP) recorded from the subthalamic nucleus in patients with Parkinson's disease (PD) demonstrate prominent oscillations in the beta (13-30 Hz) frequency range, and reduction of beta band spectral power by levodopa and deep brain stimulation (DBS) is correlated with motor symptom improvement. Several features of beta activity have been theorized to be specific biomarkers of the parkinsonian state, though these have rarely been studied in non-parkinsonian conditions. To compare resting state LFP features in PD and isolated dystonia and evaluate disease-specific biomarkers, we recorded subthalamic LFPs from 28 akinetic-rigid PD and 12 isolated dystonia patients during awake DBS implantation. Spectral power and phase-amplitude coupling characteristics were analyzed. In 26/28 PD and 11/12 isolated dystonia patients, the LFP power spectrum had a peak in the beta frequency range, with similar amplitudes between groups. Resting state power did not differ between groups in the theta (5-8 Hz), alpha (8-12 Hz), beta (13-30 Hz), broadband gamma (50-200 Hz), or high frequency oscillation (HFO, 250-350 Hz) bands. Analysis of phase-amplitude coupling between low frequency phase and HFO amplitude revealed significant interactions in 19/28 PD and 6/12 dystonia recordings without significant differences in maximal coupling or preferred phase. Two features of subthalamic LFPs that have been proposed as specific parkinsonian biomarkers, beta power and coupling of beta phase to HFO amplitude, were also present in isolated dystonia, including focal dystonias. This casts doubt on the utility of these metrics as disease-specific diagnostic biomarkers.

  10. Red and NIR light dosimetry in the human deep brain.

    PubMed

    Pitzschke, A; Lovisa, B; Seydoux, O; Zellweger, M; Pfleiderer, M; Tardy, Y; Wagnières, G

    2015-04-07

    Photobiomodulation (PBM) appears promising to treat the hallmarks of Parkinson's Disease (PD) in cellular or animal models. We measured light propagation in different areas of PD-relevant deep brain tissue during transcranial, transsphenoidal illumination (at 671 and 808 nm) of a cadaver head and modeled optical parameters of human brain tissue using Monte-Carlo simulations. Gray matter, white matter, cerebrospinal fluid, ventricles, thalamus, pons, cerebellum and skull bone were processed into a mesh of the skull (158 × 201 × 211 voxels; voxel side length: 1 mm). Optical parameters were optimized from simulated and measured fluence rate distributions. The estimated μeff for the different tissues was in all cases larger at 671 than at 808 nm, making latter a better choice for light delivery in the deep brain. Absolute values were comparable to those found in the literature or slightly smaller. The effective attenuation in the ventricles was considerably larger than literature values. Optimization yields a new set of optical parameters better reproducing the experimental data. A combination of PBM via the sphenoid sinus and oral cavity could be beneficial. A 20-fold higher efficiency of light delivery to the deep brain was achieved with ventricular instead of transcranial illumination. Our study demonstrates that it is possible to illuminate deep brain tissues transcranially, transsphenoidally and via different application routes. This opens therapeutic options for sufferers of PD or other cerebral diseases necessitating light therapy.

  11. Uncovering the mechanism(s) of deep brain stimulation

    NASA Astrophysics Data System (ADS)

    Gang, Li; Chao, Yu; Ling, Lin; C-Y Lu, Stephen

    2005-01-01

    Deep brain stimulators, often called `pacemakers for the brain', are implantable devices which continuously deliver impulse stimulation to specific targeted nuclei of deep brain structure, namely deep brain stimulation (DBS). To date, deep brain stimulation (DBS) is the most effective clinical technique for the treatment of several medically refractory movement disorders (e.g., Parkinson's disease, essential tremor, and dystonia). In addition, new clinical applications of DBS for other neurologic and psychiatric disorders (e.g., epilepsy and obsessive-compulsive disorder) have been put forward. Although DBS has been effective in the treatment of movement disorders and is rapidly being explored for the treatment of other neurologic disorders, the scientific understanding of its mechanisms of action remains unclear and continues to be debated in the scientific community. Optimization of DBS technology for present and future therapeutic applications will depend on identification of the therapeutic mechanism(s) of action. The goal of this review is to address our present knowledge of the effects of high-frequency stimulation within the central nervous system and comment on the functional implications of this knowledge for uncovering the mechanism(s) of DBS.

  12. Red and NIR light dosimetry in the human deep brain

    NASA Astrophysics Data System (ADS)

    Pitzschke, A.; Lovisa, B.; Seydoux, O.; Zellweger, M.; Pfleiderer, M.; Tardy, Y.; Wagnières, G.

    2015-04-01

    Photobiomodulation (PBM) appears promising to treat the hallmarks of Parkinson’s Disease (PD) in cellular or animal models. We measured light propagation in different areas of PD-relevant deep brain tissue during transcranial, transsphenoidal illumination (at 671 and 808 nm) of a cadaver head and modeled optical parameters of human brain tissue using Monte-Carlo simulations. Gray matter, white matter, cerebrospinal fluid, ventricles, thalamus, pons, cerebellum and skull bone were processed into a mesh of the skull (158 × 201 × 211 voxels; voxel side length: 1 mm). Optical parameters were optimized from simulated and measured fluence rate distributions. The estimated μeff for the different tissues was in all cases larger at 671 than at 808 nm, making latter a better choice for light delivery in the deep brain. Absolute values were comparable to those found in the literature or slightly smaller. The effective attenuation in the ventricles was considerably larger than literature values. Optimization yields a new set of optical parameters better reproducing the experimental data. A combination of PBM via the sphenoid sinus and oral cavity could be beneficial. A 20-fold higher efficiency of light delivery to the deep brain was achieved with ventricular instead of transcranial illumination. Our study demonstrates that it is possible to illuminate deep brain tissues transcranially, transsphenoidally and via different application routes. This opens therapeutic options for sufferers of PD or other cerebral diseases necessitating light therapy.

  13. [Deep brain stimulation. New target areas and new indications].

    PubMed

    Reich, M M; Kühn, A A; Volkmann, J

    2013-08-01

    Many patients with neurological movement disorders and psychiatric diseases cannot yet be adequately treated with conventional methods. Deep brain stimulation represents an important extension of therapeutic options by which invasive electrodes are implanted in various subcortical brain areas in order to achieve an improvement in motor and psychiatric symptoms by high frequency stimulation. Up to 2012 approximately 100,000 patients had been treated with deep brain stimulation worldwide. The indications for deep brain stimulation were essentially already established indications, such as idiopathic Parkinson's syndrome, dystonia and tremors. The newer indications which include in particular psychiatric symptoms, such as depression, obsessive diseases, addiction and Tourette syndrome, are as yet limited to approximately 5 % of treated patients. An increasingly better understanding of the system physiology of neurological and psychiatric diseases has promoted the search for new target areas and indications for treatment by neuromodulation. This article gives an overview of the latest developments in the established and also the developing application areas of deep brain stimulation.

  14. Deep brain stimulation of the subthalamic nucleus in advanced Parkinson's disease: five year follow-up at a Portuguese center.

    PubMed

    Monteiro, Ana; Andrade, Carlos; Rosas, Maria J; Linhares, Paulo; Massano, João; Vaz, Rui; Garrett, Carolina

    2014-05-16

    Introduccion. La estimulacion cerebral profunda (ECP) del nucleo subtalamico (NST) en la enfermedad de Parkinson (EP) es segura y eficaz: en la mayoria de series se describen respuestas motoras duraderas y estables. Objetivo. Informar sobre el desenlace a largo plazo de la ECP del NST en pacientes con EP avanzada atendidos en un centro hospitalario portugues. Pacientes y metodos. El estado motor se valoro con la escala unificada de valoracion de la enfermedad de Parkinson, parte III, antes de la intervencion quirurgica –en dos situaciones: sin efecto de la medicacion (off) y bajo el mejor efecto (on)–, en el postoperatorio y al cabo de cinco años (medicacion y estimulacion en on). Se cuantificaron las puntuaciones de cada sintoma axial. La incapacidad se evaluo con la escala de Rankin modificada (mRS). La aparicion de demencia se valoro seis meses y cinco años despues de la ECP. Resultados. Setenta y uno de los 183 pacientes sometidos a la ECP del NST concluyeron los cinco años de seguimiento. Diez de ellos quedaron excluidos: dos por fallecimiento (cancer e infarto de miocardio), cinco por perdida de seguimiento y tres por la retirada del sistema de estimulacion. La funcion motora manifesto una mejora del 78% en el postoperatorio y del 66% a los cinco años. En el postoperatorio se aprecio mejoria de los sintomas axiales, pero al cabo de los cinco años habian empeorado de manera significativa (p < 0,001). Las puntuaciones de la mRS tambien mejoraron en el postoperatorio, pero a los cinco años tambien habian disminuido, pese a que la mayoria (88,5%) conservaba la capacidad ambulatoria (mRS < 4). Un paciente (1,6%) manifesto demencia a los seis meses, mientras que otros 19 (31,2%) la manifestaron al cabo de los cinco años. La edad de los pacientes dementes era notablemente mayor (56,5 ± 7,8 frente a 63,7 ± 5,9 años; p < 0,001). Conclusiones. En esta serie de casos, la ECP del NST demostro su eficacia en la mejora de los sintomas motores, aunque habian transcurrido cinco años desde la implantacion. En ese periodo hubo un deterioro de los sintomas axiales y de la incapacidad, y surgieron casos de demencia, pero el posible papel de la ECP del NST como factor causal resta pendiente de concretar.

  15. Brain tumor classification of microscopy images using deep residual learning

    NASA Astrophysics Data System (ADS)

    Ishikawa, Yota; Washiya, Kiyotada; Aoki, Kota; Nagahashi, Hiroshi

    2016-12-01

    The crisis rate of brain tumor is about one point four in ten thousands. In general, cytotechnologists take charge of cytologic diagnosis. However, the number of cytotechnologists who can diagnose brain tumors is not sufficient, because of the necessity of highly specialized skill. Computer-Aided Diagnosis by computational image analysis may dissolve the shortage of experts and support objective pathological examinations. Our purpose is to support a diagnosis from a microscopy image of brain cortex and to identify brain tumor by medical image processing. In this study, we analyze Astrocytes that is a type of glia cell of central nerve system. It is not easy for an expert to discriminate brain tumor correctly since the difference between astrocytes and low grade astrocytoma (tumors formed from Astrocyte) is very slight. In this study, we present a novel method to segment cell regions robustly using BING objectness estimation and to classify brain tumors using deep convolutional neural networks (CNNs) constructed by deep residual learning. BING is a fast object detection method and we use pretrained BING model to detect brain cells. After that, we apply a sequence of post-processing like Voronoi diagram, binarization, watershed transform to obtain fine segmentation. For classification using CNNs, a usual way of data argumentation is applied to brain cells database. Experimental results showed 98.5% accuracy of classification and 98.2% accuracy of segmentation.

  16. Deep Brain Stimulation for Tremor Tractographic Versus Traditional (DISTINCT): Study Protocol of a Randomized Controlled Feasibility Trial.

    PubMed

    Sajonz, Bastian Elmar Alexander; Amtage, Florian; Reinacher, Peter Christoph; Jenkner, Carolin; Piroth, Tobias; Kätzler, Jürgen; Urbach, Horst; Coenen, Volker Arnd

    2016-12-22

    Essential tremor is a movement disorder that can result in profound disability affecting the quality of life. Medically refractory essential tremor can be successfully reduced by deep brain stimulation (DBS) traditionally targeting the thalamic ventral intermediate nucleus (Vim). Although this structure can be identified with magnetic resonance (MR) imaging nowadays, Vim-DBS electrodes are still implanted in the awake patient with intraoperative tremor testing to achieve satisfactory tremor control. This can be attributed to the fact that the more effective target of DBS seems to be the stimulation of fiber tracts rather than subcortical nuclei like the Vim. There is evidence that current coverage of the dentatorubrothalamic tract (DRT) results in good tremor control in Vim-DBS. Diffusion tensor MR imaging (DTI) tractography-assisted stereotactic surgery targeting the DRT would therefore not rely on multiple trajectories and intraoperative tremor testing in the awake patient, bearing the potential of more patient comfort and reduced operation-related risks. This is the first randomized controlled trial comparing DTI tractography-assisted stereotactic surgery targeting the DRT in general anesthesia with stereotactic surgery of thalamic/subthalamic region as conventionally used. This clinical pilot trial aims at demonstrating safety of DTI tractography-assisted stereotactic surgery in general anesthesia and proving its equality compared to conventional stereotactic surgery with intraoperative testing in the awake patient. The Deep Brain Stimulation for Tremor Tractographic Versus Traditional (DISTINCT) trial is a single-center investigator-initiated, randomized, controlled, observer-blinded trial. A total of 24 patients with medically refractory essential tremor will be randomized to either DTI tractography-assisted stereotactic surgery targeting the DRT in general anesthesia or stereotactic surgery of the thalamic/subthalamic region as conventionally used. The

  17. Deep Brain Stimulation for Tremor Tractographic Versus Traditional (DISTINCT): Study Protocol of a Randomized Controlled Feasibility Trial

    PubMed Central

    Reinacher, Peter Christoph; Jenkner, Carolin; Piroth, Tobias; Kätzler, Jürgen; Urbach, Horst; Coenen, Volker Arnd

    2016-01-01

    Background Essential tremor is a movement disorder that can result in profound disability affecting the quality of life. Medically refractory essential tremor can be successfully reduced by deep brain stimulation (DBS) traditionally targeting the thalamic ventral intermediate nucleus (Vim). Although this structure can be identified with magnetic resonance (MR) imaging nowadays, Vim-DBS electrodes are still implanted in the awake patient with intraoperative tremor testing to achieve satisfactory tremor control. This can be attributed to the fact that the more effective target of DBS seems to be the stimulation of fiber tracts rather than subcortical nuclei like the Vim. There is evidence that current coverage of the dentatorubrothalamic tract (DRT) results in good tremor control in Vim-DBS. Diffusion tensor MR imaging (DTI) tractography-assisted stereotactic surgery targeting the DRT would therefore not rely on multiple trajectories and intraoperative tremor testing in the awake patient, bearing the potential of more patient comfort and reduced operation-related risks. This is the first randomized controlled trial comparing DTI tractography-assisted stereotactic surgery targeting the DRT in general anesthesia with stereotactic surgery of thalamic/subthalamic region as conventionally used. Objective This clinical pilot trial aims at demonstrating safety of DTI tractography-assisted stereotactic surgery in general anesthesia and proving its equality compared to conventional stereotactic surgery with intraoperative testing in the awake patient. Methods The Deep Brain Stimulation for Tremor Tractographic Versus Traditional (DISTINCT) trial is a single-center investigator-initiated, randomized, controlled, observer-blinded trial. A total of 24 patients with medically refractory essential tremor will be randomized to either DTI tractography-assisted stereotactic surgery targeting the DRT in general anesthesia or stereotactic surgery of the thalamic/subthalamic region as

  18. Activity Parameters of Subthalamic Nucleus Neurons Selectively Predict Motor Symptom Severity in Parkinson's Disease

    PubMed Central

    Gulberti, Alessandro; Zittel, Simone; Tudor Jones, Adam A.; Fickel, Ulrich; Münchau, Alexander; Köppen, Johannes A.; Gerloff, Christian; Westphal, Manfred; Buhmann, Carsten; Hamel, Wolfgang; Engel, Andreas K.

    2014-01-01

    Parkinson's disease (PD) is a heterogeneous disorder that leads to variable expression of several different motor symptoms. While changes in firing rate, pattern, and oscillation of basal ganglia neurons have been observed in PD patients and experimental animals, there is limited evidence linking them to specific motor symptoms. Here we examined this relationship using extracellular recordings of subthalamic nucleus neurons from 19 PD patients undergoing surgery for deep brain stimulation. For each patient, ≥10 single units and/or multi-units were recorded in the OFF medication state. We correlated the proportion of neurons displaying different activities with preoperative Unified Parkinson's Disease Rating Scale subscores (OFF medication). The mean spectral power at sub-beta frequencies and percentage of units oscillating at beta frequencies were positively correlated with the axial and limb rigidity scores, respectively. The percentage of units oscillating at gamma frequency was negatively correlated with the bradykinesia scores. The mean intraburst rate was positively correlated with both bradykinesia and axial scores, while the related ratio of interspike intervals below/above 10 ms was positively correlated with these symptoms and limb rigidity. None of the activity parameters correlated with tremor. The grand average of all the significantly correlated subthalamic nucleus activities accounted for >60% of the variance of the combined bradykinetic-rigid and axial scores. Our results demonstrate that the occurrence of alterations in the rate and pattern of basal ganglia neurons could partly underlie the variability in parkinsonian phenotype. PMID:24790198

  19. Activity parameters of subthalamic nucleus neurons selectively predict motor symptom severity in Parkinson's disease.

    PubMed

    Sharott, Andrew; Gulberti, Alessandro; Zittel, Simone; Tudor Jones, Adam A; Fickel, Ulrich; Münchau, Alexander; Köppen, Johannes A; Gerloff, Christian; Westphal, Manfred; Buhmann, Carsten; Hamel, Wolfgang; Engel, Andreas K; Moll, Christian K E

    2014-04-30

    Parkinson's disease (PD) is a heterogeneous disorder that leads to variable expression of several different motor symptoms. While changes in firing rate, pattern, and oscillation of basal ganglia neurons have been observed in PD patients and experimental animals, there is limited evidence linking them to specific motor symptoms. Here we examined this relationship using extracellular recordings of subthalamic nucleus neurons from 19 PD patients undergoing surgery for deep brain stimulation. For each patient, ≥ 10 single units and/or multi-units were recorded in the OFF medication state. We correlated the proportion of neurons displaying different activities with preoperative Unified Parkinson's Disease Rating Scale subscores (OFF medication). The mean spectral power at sub-beta frequencies and percentage of units oscillating at beta frequencies were positively correlated with the axial and limb rigidity scores, respectively. The percentage of units oscillating at gamma frequency was negatively correlated with the bradykinesia scores. The mean intraburst rate was positively correlated with both bradykinesia and axial scores, while the related ratio of interspike intervals below/above 10 ms was positively correlated with these symptoms and limb rigidity. None of the activity parameters correlated with tremor. The grand average of all the significantly correlated subthalamic nucleus activities accounted for >60% of the variance of the combined bradykinetic-rigid and axial scores. Our results demonstrate that the occurrence of alterations in the rate and pattern of basal ganglia neurons could partly underlie the variability in parkinsonian phenotype.

  20. Low-frequency Subthalamic Stimulation in Parkinson's Disease: Long-term Outcome and Predictors.

    PubMed

    Zibetti, Maurizio; Moro, Elena; Krishna, Vibhor; Sammartino, Francesco; Picillo, Marina; Munhoz, Renato P; Lozano, Andres M; Fasano, Alfonso

    2016-01-01

    Parkinson's disease patients undergoing subthalamic nucleus deep brain stimulation (STN DBS) at standard frequency (>100 Hz) often develop gait impairment, postural instability and speech difficulties. Low frequency stimulation (<100 Hz, LFS) can improve such axial symptoms, but there are concerns that improvement may be transient. To identify long-term outcome and predictors of low-frequency subthalamic stimulation in Parkinson's disease. Through a chart review we identified 85 out of 324 STN DBS patients who received a trial of LFS and describe their characteristics and outcome predictors. Patients were switched to LFS (<100 Hz) 3.8 ± 3.3 years after surgery. Most patients (64%) attained a subjective improvement of gait, speech or balance for 2.0 ± 1.9 years. Motor scores improved within the first year after the stimulation change and showed a slower progression over time when compared to patients switched back to high frequency stimulation. UPDRS III axial score on medication before surgery and the y-axis coordinate of the active contact were independent predictors of LFS retention. This report provides evidence that the use of LFS yields an enduring benefit in a considerable percentage of patients who develop axial motor symptoms during conventional stimulation. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Sensory contribution to vocal emotion deficit in Parkinson’s disease after subthalamic stimulation

    PubMed Central

    Péron, Julie; Cekic, Sezen; Haegelen, Claire; Sauleau, Paul; Patel, Sona; Drapier, Dominique; Vérin, Marc; Grandjean, Didier

    2016-01-01

    Subthalamic nucleus (STN) deep brain stimulation in Parkinson’s disease induces modifications in the recognition of emotion from voices (or emotional prosody). Nevertheless, the underlying mechanisms are still only poorly understood, and the role of acoustic features in these deficits has yet to be elucidated. Our aim was to identify the influence of acoustic features on changes in emotional prosody recognition following STN stimulation in Parkinson’s disease. To this end, we analysed the performances of patients on vocal emotion recognition in pre-versus post-operative groups, as well as of matched controls, entering the acoustic features of the stimuli into our statistical models. Analyses revealed that the post-operative biased ratings on the Fear scale when patients listened to happy stimuli were correlated with loudness, while the biased ratings on the Sadness scale when they listened to happiness were correlated with fundamental frequency (F0). Furthermore, disturbed ratings on the Happiness scale when the post-operative patients listened to sadness were found to be correlated with F0. These results suggest that inadequate use of acoustic features following subthalamic stimulation has a significant impact on emotional prosody recognition in patients with Parkinson’s disease, affecting the extraction and integration of acoustic cues during emotion perception. PMID:25282055

  2. Comparison of oscillatory activity in subthalamic nucleus in Parkinson's disease and dystonia

    PubMed Central

    Jiang, Yin; Ashkan, Keyoumars; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Green, Alexander; Aziz, Tipu; Brown, Peter; Wang, Shouyan

    2017-01-01

    Objectives Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been successfully used to treat both Parkinson's disease (PD) and dystonia. Local field potentials (LFPs) recorded from the STN of PD patients demonstrate prominent beta frequency band activity. It is unclear whether such activity occurs in the STN in dystonia, and, if not, whether dystonia has another distinctive neural population activity in the STN. Methods Twelve patients with PD, and eight patients with dystonia underwent DBS electrode implantation targeting the STN. Seven dystonia patients were off medication and one was on aripiprazole and clonazepam. LFPs were recorded from the DBS electrodes in PD in the on/off medication states and in dystonia. Power spectra and temporal dynamics measured by the with Lempel-Ziv complexity of the LFPs were compared among these states. Results Normalised power spectra and Lempel-Ziv complexity of subthalamic LFPs differed between dystonia off and PD on/off, and between PD off and on over the low frequency, beta and high gamma bands. Patients with dystonia and off medication had lower beta power but higher low frequency and high gamma power than PD. Spectral power in the low beta frequency (11–20 Hz) range was attenuated in medicated PD. Conclusion The results suggest that dystonia and PD are characterized by different patterns of oscillatory activities even within the same nucleus, and exaggerated beta activity may relate to hypo-dopaminergic status. PMID:27940307

  3. Optogenetic Tools for Confined Stimulation in Deep Brain Structures.

    PubMed

    Castonguay, Alexandre; Thomas, Sébastien; Lesage, Frédéric; Casanova, Christian

    2016-01-01

    Optogenetics has emerged in the past decade as a technique to modulate brain activity with cell-type specificity and with high temporal resolution. Among the challenges associated with this technique is the difficulty to target a spatially restricted neuron population. Indeed, light absorption and scattering in biological tissues make it difficult to illuminate a minute volume, especially in the deep brain, without the use of optical fibers to guide light. This work describes the design and the in vivo application of a side-firing optical fiber adequate for delivering light to specific regions within a brain subcortical structure.

  4. Deep brain stimulator infection by a novel rapid growing mycobacterium.

    PubMed

    Moritz, Donna C; Harrington, Amanda T; Slavin, Konstantin; Gomez, Christy; Jarrett, Olamide D

    2017-09-20

    Devise-related infections after deep brain stimulator implantation are not uncommon. However, infections due to mycobacteria have not been reported in the medical literature. We describe the first reported case of DBS infection due to a novel rapidly growing mycobacteria, most closely resembling Mycobacterium goodii, by rpoB gene sequencing.

  5. A Non-Invasive Imaging Approach to Understanding Speech Changes following Deep Brain Stimulation in Parkinson’s Disease

    PubMed Central

    Narayana, Shalini; Jacks, Adam; Robin, Donald A.; Poizner, Howard; Zhang, Wei; Franklin, Crystal; Liotti, Mario; Vogel, Deanie; Fox, Peter T.

    2009-01-01

    Purpose To explore the use of non-invasive functional imaging and “virtual” lesion techniques to study the neural mechanisms underlying motor speech disorders in Parkinson’s disease. Here, we report the use of Positron Emission Tomography (PET) and transcranial magnetic stimulation (TMS) to explain exacerbated speech impairment following subthalamic nucleus deep brain stimulation (STN-DBS) in a patient with Parkinson’s disease. Method Perceptual and acoustic speech measures as well as cerebral blood flow (CBF) during speech as measured by PET were obtained with STN-DBS on and off. TMS was applied to a region in the speech motor network found to be abnormally active during DBS. Speech disruption by TMS was compared both perceptually and acoustically with that resulting from DBS on. Results Speech production was perceptually inferior and acoustically less contrastive during left STN stimulation compared to no stimulation. Increased neural activity in left dorsal premotor cortex (PMd) was observed during DBS on. “Virtual” lesioning of this region resulted in speech characterized by decreased speech segment duration, increased pause duration, and decreased intelligibility. Conclusions This case report provides evidence that impaired speech production accompanying STN-DBS may be resulting from unintended activation of PMd. Clinical application of functional imaging and TMS may lead to optimizing the delivery of STN-DBS to improve outcomes for speech production as well as general motor abilities. PMID:19029533

  6. Axonal and synaptic failure suppress the transfer of firing rate oscillations, synchrony and information during high frequency deep brain stimulation.

    PubMed

    Rosenbaum, Robert; Zimnik, Andrew; Zheng, Fang; Turner, Robert S; Alzheimer, Christian; Doiron, Brent; Rubin, Jonathan E

    2014-02-01

    High frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a widely used treatment for Parkinson's disease, but its effects on neural activity in basal ganglia circuits are not fully understood. DBS increases the excitation of STN efferents yet decouples STN spiking patterns from the spiking patterns of STN synaptic targets. We propose that this apparent paradox is resolved by recent studies showing an increased rate of axonal and synaptic failures in STN projections during DBS. To investigate this hypothesis, we combine in vitro and in vivo recordings to derive a computational model of axonal and synaptic failure during DBS. Our model shows that these failures induce a short term depression that suppresses the synaptic transfer of firing rate oscillations, synchrony and rate-coded information from STN to its synaptic targets. In particular, our computational model reproduces the widely reported suppression of parkinsonian β oscillations and synchrony during DBS. Our results support the idea that short term depression is a therapeutic mechanism of STN DBS that works as a functional lesion by decoupling the somatic spiking patterns of STN neurons from spiking activity in basal ganglia output nuclei.

  7. Radiofrequency Lesions through Deep Brain Stimulation Electrodes in Movement Disorders: Case Report and Review of the Literature.

    PubMed

    Pérez-Suárez, Javier; Torres Díaz, Cristina V; López Manzanares, Lydia; Navas García, Marta; Pastor, Jesús; Barrio Fernández, Patricia; G de Sola, Rafael

    2017-01-01

    Although there are few reports of radiofrequency lesions performed through deep brain stimulation (DBS) electrodes in patients with movement disorders, experience with this method is scarce. We present 2 patients who had been previously treated with DBS of subthalamic nuclei (STN) and the ventral intermediate (VIM) nucleus of the thalamus for Parkinson's disease and essential tremor, respectively, and underwent a radiofrequency lesion through their DBS electrodes after developing a hardware infection. The authors conduct a review of the literature regarding this method. Both patients had a good clinical outcome after 20 and 8 months, respectively, as assessed by a reduction in Fahn-Tolosa-Marin Scale and Unified Parkinson's Disease Rating Scale scores. The second patient underwent a second DBS system implantation surgery after his radiofrequency treatment to optimize his management, achieving optimal clinical control with lower current and drug requirements than before the radiofrequency intervention. No adverse effects were observed. Radiofrequency lesions through DBS electrodes allow the creation of small and localized lesions. Its effectiveness and low-risk profile, in addition to its low cost, make this procedure suitable and a possible alternative in the therapeutic repertoire for the surgical treatment of movement disorders. © 2017 S. Karger AG, Basel.

  8. Patient-specific models of deep brain stimulation: Influence of field model complexity on neural activation predictions

    PubMed Central

    Chaturvedi, Ashutosh; Butson, Christopher R.; Lempka, Scott F.; Cooper, Scott E.; McIntyre, Cameron C.

    2010-01-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become the surgical therapy of choice for medically intractable Parkinson’s disease. However, quantitative understanding of the interaction between the electric field generated by DBS and the underlying neural tissue is limited. Recently, computational models of varying levels of complexity have been used to study the neural response to DBS. The goal of this study was to evaluate the quantitative impact of incrementally incorporating increasing levels of complexity into computer models of STN DBS. Our analysis focused on the direct activation of experimentally measureable fiber pathways within the internal capsule (IC). Our model system was customized to an STN DBS patient and stimulation thresholds for activation of IC axons were calculated with electric field models that ranged from an electrostatic, homogenous, isotropic model to one that explicitly incorporated the voltage-drop and capacitance of the electrode-electrolyte interface, tissue encapsulation of the electrode, and diffusion-tensor based 3D tissue anisotropy and inhomogeneity. The model predictions were compared to experimental IC activation defined from electromyographic (EMG) recordings from eight different muscle groups in the contralateral arm and leg of the STN DBS patient. Coupled evaluation of the model and experimental data showed that the most realistic predictions of axonal thresholds were achieved with the most detailed model. Furthermore, the more simplistic neurostimulation models substantially overestimated the spatial extent of neural activation. PMID:20607090

  9. Deep brain stimulation of the globus pallidus internus and Gilles de la Tourette syndrome: Toward multiple networks modulation.

    PubMed

    Saleh, Christian; Gonzalez, Victoria; Cif, Laura; Coubes, Philippe

    2012-01-01

    Gilles de la Tourette's syndrome (GTS) is a complex neuropsychiatric disorder characterized by disabling motor and vocal tics. The pathophysiology of GTS remains poorly understood. Conventional treatment consists in pharmacological and behavioral treatment. For patients suffering severe adverse effects or not responding to pharmacological treatment, deep brain stimulation (DBS) presents an alternative treatment. However, the optimal target choice in DBS for GTS remains a divisive issue. A PubMed search from 1999 to 2012 was conducted. Thirty-three research articles reporting on DBS in patients with GTS were selected and analyzed. Eighty-eight patients with Tourette's syndrome were treated since 1999 with DBS. The majority of patients received thalamic stimulation. Significantly fewer patients were treated with globus pallidus internus stimulation. Occasionally, the anterior limb of the internal capsule and the nucleus accumbens were implanted. The subthalamic nucleus was selected once. All targets were reported with positive results, but of variable extent. Only 14 patients exhibited level 1 evidence. In light of the wide spectrum of associated behavioral co-morbidities in GTS, multiple networks modulation may result in the most efficacious treatment strategy. The optimal locations for DBS within the cortico-basal ganglia-thalamocortical circuits remain to be established. However, at the current stage, comparison between targets should be done with great caution. Significant disparity between number of patients treated per target, methodological variability, and quality of reporting renders a meaningful comparison between targets difficult. Randomized controlled trials with larger cohorts and standardization of procedures are urgently needed.

  10. Frequency-selectivity of a thalamocortical relay neuron during Parkinson's disease and deep brain stimulation: a computational study.

    PubMed

    Cagnan, Hayriye; Meijer, Hil G E; van Gils, Stephan A; Krupa, Martin; Heida, Tjitske; Rudolph, Michelle; Wadman, Wytse J; Martens, Hubert C F

    2009-10-01

    In this computational study, we investigated (i) the functional importance of correlated basal ganglia (BG) activity associated with Parkinson's disease (PD) motor symptoms by analysing the effects of globus pallidus internum (GPi) bursting frequency and synchrony on a thalamocortical (TC) relay neuron, which received GABAergic projections from this nucleus; (ii) the effects of subthalamic nucleus (STN) deep brain stimulation (DBS) on the response of the TC relay neuron to synchronized GPi oscillations; and (iii) the functional basis of the inverse relationship that has been reported between DBS frequency and stimulus amplitude, required to alleviate PD motor symptoms [A. L. Benabid et al. (1991)Lancet, 337, 403-406]. The TC relay neuron selectively responded to and relayed synchronized GPi inputs bursting at a frequency located in the range 2-25 Hz. Input selectivity of the TC relay neuron is dictated by low-threshold calcium current dynamics and passive membrane properties of the neuron. STN-DBS prevented the TC relay neuron from relaying synchronized GPi oscillations to cortex. Our model indicates that DBS alters BG output and input selectivity of the TC relay neuron, providing an explanation for the clinically observed inverse relationship between DBS frequency and stimulus amplitude.

  11. Laser treatments of deep-seated brain lesions

    NASA Astrophysics Data System (ADS)

    Ward, Helen A.

    1997-06-01

    The five year survival rate of deep-seated malignant brain tumors after surgery/radiotherapy is virtually 100 percent mortality. Special problems include: (1) Lesions often present late. (2) Position: lesion overlies vital structures, so complete surgical/radiotherapy lesion destruction can damage vital brain-stem functions. (3) Difficulty in differentiating normal brain form malignant lesions. This study aimed to use the unique properties of the laser: (a) to minimize damage during surgical removal of deep-seated brain lesions by operating via fine optic fibers; and (b) to employ the propensity of certain lasers for absorption of dyes and absorption and induction of fluorescence in some brain substances, to differentiate borders of malignant and normal brain, for more complete tumor removal. In the method a fine laser endoscopic technique was devised for removal of brain lesions. The results of this technique, were found to minimize and accurately predict the extent of thermal damage and shock waves to within 1-2mm of the surgical laser beam. Thereby it eliminated the 'popcorn' effect.

  12. Long-range correlation properties in timing of skilled piano performance: the influence of auditory feedback and deep brain stimulation.

    PubMed

    Herrojo Ruiz, María; Hong, Sang Bin; Hennig, Holger; Altenmüller, Eckart; Kühn, Andrea A

    2014-01-01

    Unintentional timing deviations during musical performance can be conceived of as timing errors. However, recent research on humanizing computer-generated music has demonstrated that timing fluctuations that exhibit long-range temporal correlations (LRTC) are preferred by human listeners. This preference can be accounted for by the ubiquitous presence of LRTC in human tapping and rhythmic performances. Interestingly, the manifestation of LRTC in tapping behavior seems to be driven in a subject-specific manner by the LRTC properties of resting-state background cortical oscillatory activity. In this framework, the current study aimed to investigate whether propagation of timing deviations during the skilled, memorized piano performance (without metronome) of 17 professional pianists exhibits LRTC and whether the structure of the correlations is influenced by the presence or absence of auditory feedback. As an additional goal, we set out to investigate the influence of altering the dynamics along the cortico-basal-ganglia-thalamo-cortical network via deep brain stimulation (DBS) on the LRTC properties of musical performance. Specifically, we investigated temporal deviations during the skilled piano performance of a non-professional pianist who was treated with subthalamic-deep brain stimulation (STN-DBS) due to severe Parkinson's disease, with predominant tremor affecting his right upper extremity. In the tremor-affected right hand, the timing fluctuations of the performance exhibited random correlations with DBS OFF. By contrast, DBS restored long-range dependency in the temporal fluctuations, corresponding with the general motor improvement on DBS. Overall, the present investigations demonstrate the presence of LRTC in skilled piano performances, indicating that unintentional temporal deviations are correlated over a wide range of time scales. This phenomenon is stable after removal of the auditory feedback, but is altered by STN-DBS, which suggests that cortico

  13. Long-range correlation properties in timing of skilled piano performance: the influence of auditory feedback and deep brain stimulation

    PubMed Central

    Herrojo Ruiz, María; Hong, Sang Bin; Hennig, Holger; Altenmüller, Eckart; Kühn, Andrea A.

    2014-01-01

    Unintentional timing deviations during musical performance can be conceived of as timing errors. However, recent research on humanizing computer-generated music has demonstrated that timing fluctuations that exhibit long-range temporal correlations (LRTC) are preferred by human listeners. This preference can be accounted for by the ubiquitous presence of LRTC in human tapping and rhythmic performances. Interestingly, the manifestation of LRTC in tapping behavior seems to be driven in a subject-specific manner by the LRTC properties of resting-state background cortical oscillatory activity. In this framework, the current study aimed to investigate whether propagation of timing deviations during the skilled, memorized piano performance (without metronome) of 17 professional pianists exhibits LRTC and whether the structure of the correlations is influenced by the presence or absence of auditory feedback. As an additional goal, we set out to investigate the influence of altering the dynamics along the cortico-basal-ganglia-thalamo-cortical network via deep brain stimulation (DBS) on the LRTC properties of musical performance. Specifically, we investigated temporal deviations during the skilled piano performance of a non-professional pianist who was treated with subthalamic-deep brain stimulation (STN-DBS) due to severe Parkinson's disease, with predominant tremor affecting his right upper extremity. In the tremor-affected right hand, the timing fluctuations of the performance exhibited random correlations with DBS OFF. By contrast, DBS restored long-range dependency in the temporal fluctuations, corresponding with the general motor improvement on DBS. Overall, the present investigations demonstrate the presence of LRTC in skilled piano performances, indicating that unintentional temporal deviations are correlated over a wide range of time scales. This phenomenon is stable after removal of the auditory feedback, but is altered by STN-DBS, which suggests that cortico

  14. Neurosurgery of the future: Deep brain stimulations and manipulations.

    PubMed

    Nicolaidis, Stylianos

    2017-04-01

    Important advances are afoot in the field of neurosurgery-particularly in the realms of deep brain stimulation (DBS), deep brain manipulation (DBM), and the newly introduced refinement "closed-loop" deep brain stimulation (CLDBS). Use of closed-loop technol